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Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: KIAA1024L.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of this gene to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Classified gene: KIAA1024L as Amber List (moderate evidence)
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene to green rating in the next GMS review.
Monogenic hearing loss v4.38 KIAA1024L Achchuthan Shanmugasundram Gene: kiaa1024l has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.37 KIAA1024L Achchuthan Shanmugasundram commented on gene: KIAA1024L: The new gene name for KIAA1024L is MINAR2 and 'new-gene-name' tag has been added to flag this.
Monogenic hearing loss v4.37 KIAA1024L Achchuthan Shanmugasundram gene: KIAA1024L was added
gene: KIAA1024L was added to Monogenic hearing loss. Sources: Literature
new-gene-name tags were added to gene: KIAA1024L.
Mode of inheritance for gene: KIAA1024L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1024L were set to 35727972
Phenotypes for gene: KIAA1024L were set to Deafness, autosomal recessive 120, OMIM:620238
Review for gene: KIAA1024L was set to GREEN
Added comment: PMID:35727972 reported 13 patients from four unrelated families with non-syndromic sensorineural hearing loss. Four of these patients had prelingual onset of severe to profound, progressive bilateral hearing loss. The other nine patients had congenital onset of severe to profound bilateral hearing loss, which was not progressive on one patient, while data was not available for the other.

Three different homozygous variants (c.144G > A/ p.Trp48Ter, c.412_419delCGGTTTTG/ p.Arg138Valfs*10 and c.393G > T/ p.Lys131Asn) were identified in MINAR2/ KIAA1024L gene in these patients.

There is some functional evidence available for the p.Lys131Asn variant. In addition, mice with loss of function of the Minar2 protein present with rapidly progressive sensorineural hearing loss.

This gene has also been associated with relevant phenotype in OMIM (MIM #620238).
Sources: Literature
Monogenic hearing loss v4.36 GRXCR2 Sadaf Naz reviewed gene: GRXCR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33528103, PMID:24619944; Phenotypes: #615837: Deafness, autosomal recessive 101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram commented on gene: GRAP: As reviewed by Barbara Vona, two unrelated families were reported with the same homozygous missense variant. There is some functional data available as well.

This gene has been associated with relevant phenotype in OMIM (MIM #618456).
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram Classified gene: GRAP as Red List (low evidence)
Monogenic hearing loss v4.36 GRAP Achchuthan Shanmugasundram Gene: grap has been classified as Red List (Low Evidence).
Monogenic hearing loss v4.35 GRAP Achchuthan Shanmugasundram Phenotypes for gene: GRAP were changed from Non-syndromic hearing loss to Deafness, autosomal recessive 114, OMIM:618456
Monogenic hearing loss v4.34 GRAP Achchuthan Shanmugasundram reviewed gene: GRAP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 114, OMIM:618456; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.34 GRAP Achchuthan Shanmugasundram Publications for gene: GRAP were set to PMID: 30610177
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Classified gene: NLRP12 as Amber List (moderate evidence)
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases) for the association of NLRP12 with sensorineural hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.33 NLRP12 Achchuthan Shanmugasundram Gene: nlrp12 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: NLRP12.
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram changed review comment from: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.
Sources: Literature; to: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.

NLRP12 has been associated with Familial cold autoinflammatory syndrome 2 (MIM #611762) in OMIM and sensorineural deafness has been listed as one of the clinical presentations of this phenotype.

Sources: Literature
Monogenic hearing loss v4.32 NLRP12 Achchuthan Shanmugasundram gene: NLRP12 was added
gene: NLRP12 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: NLRP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP12 were set to 18230725; 24064030; 31820221
Phenotypes for gene: NLRP12 were set to Familial cold autoinflammatory syndrome 2, OMIM:611762; sensorineural hearing loss disorder, MONDO:0020678
Review for gene: NLRP12 was set to GREEN
Added comment: PMID:18230725 - Two unrelated families from Guadeloupe were reported with a periodic fever syndrome and with monoallelic NLRP12 variants. Of these, twin boys from family 1 had bilateral sensorineural hearing loss.

PMID:24064030 - Six unrelated Italian patients were reported with familial cold autoinflammatory syndrome 2 and NLRP12 variants, of which one patient had sensorineural hearing loss.

PMID:31820221 - Three cases presenting with NLRP12 - autoinflammatory disorder were reported, where one had sensorineural deafness.
Sources: Literature
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.31 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.30 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051; 32631815
Monogenic hearing loss v4.30 RIPOR2 Achchuthan Shanmugasundram Publications for gene: RIPOR2 were set to 17150207; 24958875; 9055809; 9205841; 24958875; 27269051
Monogenic hearing loss v4.29 RIPOR2 Achchuthan Shanmugasundram Phenotypes for gene: RIPOR2 were changed from Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515 to Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515
Monogenic hearing loss v4.29 RIPOR2 Achchuthan Shanmugasundram Phenotypes for gene: RIPOR2 were changed from ?Deafness, autosomal recessive 104 , OMIM:616515 to Deafness, autosomal dominant 21, OMIM:607017; ?Deafness, autosomal recessive 104, OMIM:616515
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Classified gene: RIPOR2 as Amber List (moderate evidence)
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Added comment: Comment on list classification: Only one variant was reported with both monoallelic and biallelic inheritance. There is some functional data for both modes of inheritance. Although there are 12 unrelated cases reported with the same monoallelic variant, this variant was suggested to be founder variant. Hence, this gene can only be rated amber with the current evidence for both modes of inheritance.
Monogenic hearing loss v4.28 RIPOR2 Achchuthan Shanmugasundram Gene: ripor2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram changed review comment from: Biallelic variants:
PMID:24958875 reported six affected members from a single Turkish family with a homozygous splice site variant in the RIPOR2 gene (c.102-1G-A) and with deafness. In addition, morpholino knockdown of the orthologous gene in zebrafish embryos resulted in a significant reduction in the number of saccular hair cells and neuromasts, and caused hearing loss.

Monoallelic variants:
PMID:32631815 reported a heterozygous 12 nucleotide in-frame deletion (c.1696_1707del, p.Gln566_Lys569del) in RIPOR2 that was detected in 12 families of Dutch origin with non-syndromic hearing loss.

In total, the variant was detected in 59/63 affected participants, but also in five unaffected subjects from three family. Age of onset was highly variable, from congenital to 70 years (mean age: 30.6 years) - unaffected family members who harboured the variant were aged 23, 40, 49, 50, and 51 years, respectively. The authors speculated that the four affected subjects without the variant represent phenocopies. The presence of an identical variant in 12 families of common origin, as well as haplotype analysis, indicates a founder effect.

Functional analysis of this variant showed aberrant localisation of RIPOR2 variant protein in early postnatal mouse hair cells, ex vivo; and failure to rescue the stereocilia defects of Ripor2 knockout mice, in contrast to the rescue effect observed in cells expressing wild-type RIPOR2.; to: Biallelic variants:
PMID:24958875 reported six affected members from a single Turkish family with a homozygous splice site variant in the RIPOR2 gene (c.102-1G-A) and with deafness. In addition, morpholino knockdown of the orthologous gene in zebrafish embryos resulted in a significant reduction in the number of saccular hair cells and neuromasts, and caused hearing loss.

Monoallelic variants:
PMID:32631815 reported a heterozygous 12 nucleotide in-frame deletion (c.1696_1707del, p.Gln566_Lys569del) in RIPOR2 that was detected in 12 families of Dutch origin with non-syndromic hearing loss.

In total, the variant was detected in 59/63 affected participants, but also in five unaffected subjects from three family. Age of onset was highly variable, from congenital to 70 years (mean age: 30.6 years) - unaffected family members who harboured the variant were aged 23, 40, 49, 50, and 51 years, respectively. The authors speculated that the four affected subjects without the variant represent phenocopies. The presence of an identical variant in 12 families of common origin, as well as haplotype analysis, indicates a founder effect. Hence, the 'founder-effect' tag was added.

Functional analysis of this variant showed aberrant localisation of RIPOR2 variant protein in early postnatal mouse hair cells, ex vivo; and failure to rescue the stereocilia defects of Ripor2 knockout mice, in contrast to the rescue effect observed in cells expressing wild-type RIPOR2.
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram edited their review of gene: RIPOR2: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: RIPOR2.
Monogenic hearing loss v4.27 RIPOR2 Achchuthan Shanmugasundram reviewed gene: RIPOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24958875, 32631815; Phenotypes: Deafness, autosomal dominant 21, OMIM:607017, ?Deafness, autosomal recessive 104, OMIM:616515; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v4.26 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Monogenic hearing loss v4.25 RIPOR2 Dmitrijs Rots reviewed gene: RIPOR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32631815; Phenotypes: Adult-onset hearing loss; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v4.25 COL9A3 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: COL9A3.
Tag Q2_21_phenotype was removed from gene: COL9A3.
Tag Q2_21_expert_review was removed from gene: COL9A3.
Monogenic hearing loss v4.25 FOXI1 Achchuthan Shanmugasundram Tag Q1_22_expert_review was removed from gene: FOXI1.
Tag Q1_22_MOI was removed from gene: FOXI1.
Monogenic hearing loss v4.25 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: This gene can be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.25 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Monogenic hearing loss v4.25 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.25 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.24 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with hearing loss. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Monogenic hearing loss v4.24 PSMC3 Achchuthan Shanmugasundram Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v4.23 PSMC3 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: PSMC3.
Monogenic hearing loss v4.23 PSMC3 Achchuthan Shanmugasundram gene: PSMC3 was added
gene: PSMC3 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to 32500975; 37256937
Phenotypes for gene: PSMC3 were set to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092; autosomal dominant nonsyndromic hearing loss, MONDO:0019587
Review for gene: PSMC3 was set to GREEN
Added comment: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. They were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). 9/19 patients had hearing loss, of which two were labelled as sensorineural and one was labelled as conductive. In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.
Sources: Literature
Monogenic hearing loss v4.22 PTPRQ Arina Puzriakova Phenotypes for gene: PTPRQ were changed from Deafness, autosomal recessive 84A, 613391; Deafness,autosomalrecessive84A,613391 to Deafness, autosomal dominant 73, OMIM:617663; Deafness, autosomal recessive 84A, OMIM:613391
Monogenic hearing loss v4.21 PTPRQ Arina Puzriakova Added comment: Comment on publications: Previous publications listed: "PMID: 20346435 report a homozygous variant resulting in Tyr497Ter in 2 Dutch siblings with AR nonsyndromic hearing loss, and not found in matched controls. A homozygous variant resulting in Arg457Gly identified in 2 Moroccan siblings with AR nonsyndromic hearing loss, was also not found in matched controls."
Monogenic hearing loss v4.21 PTPRQ Arina Puzriakova Publications for gene: PTPRQ were set to PMID: 20346435 report a homozygous variant resulting in Tyr497Ter in 2 Dutch siblings with AR nonsyndromic hearing loss, and not found in matched controls. A homozygous variant resulting in Arg457Gly identified in 2 Moroccan siblings with AR nonsyndromic hearing loss, was also not found in matched controls.
Monogenic hearing loss v4.18 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5
Monogenic hearing loss v4.18 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Monogenic hearing loss v4.18 SPATA5L1 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: SPATA5L1.
Monogenic hearing loss v4.18 SPATA5 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: SPATA5.
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Deleted their comment
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Deleted their comment
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Classified gene: GPR156 as Amber List (moderate evidence)
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Andrew Mumford, there are three unrelated families with biallelic (either homozygous or compound heterozygous) GPR156 variants reported with congenital nonsyndromic bilateral sensorineural hearing loss. Hence, this gene should be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Gene: gpr156 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Classified gene: GPR156 as Amber List (moderate evidence)
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Andrew Mumford, there are three unrelated families with biallelic (either homozygous or compound heterozygous) GPR156 variants reported with congenital nonsyndromic bilateral sensorineural hearing loss. Hence, this gene should be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Gene: gpr156 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Classified gene: GPR156 as Amber List (moderate evidence)
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Andrew Mumford, there are three unrelated families with biallelic (either homozygous or compound heterozygous) GPR156 variants reported with congenital nonsyndromic bilateral sensorineural hearing loss. Hence, this gene should be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.18 GPR156 Achchuthan Shanmugasundram Gene: gpr156 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.17 GPR156 Achchuthan Shanmugasundram Phenotypes for gene: GPR156 were changed from sensorineural hearing loss disorder, MONDO:0020678 to sensorineural hearing loss disorder, MONDO:0020678
Monogenic hearing loss v4.17 GPR156 Achchuthan Shanmugasundram Phenotypes for gene: GPR156 were changed from sensorineural hearing loss to sensorineural hearing loss disorder, MONDO:0020678
Monogenic hearing loss v4.16 GPR156 Achchuthan Shanmugasundram Publications for gene: GPR156 were set to 36928819
Monogenic hearing loss v4.15 GPR156 Achchuthan Shanmugasundram Publications for gene: GPR156 were set to PMID:36928829
Monogenic hearing loss v4.14 GPR156 Achchuthan Shanmugasundram Tag Q3_23_NHS_review tag was added to gene: GPR156.
Monogenic hearing loss v4.14 GPR156 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: GPR156.
Monogenic hearing loss v4.14 GPR156 Achchuthan Shanmugasundram reviewed gene: GPR156: Rating: GREEN; Mode of pathogenicity: None; Publications: 36928819; Phenotypes: sensorineural hearing loss disorder, MONDO:0020678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.14 GPR156 Andrew Mumford gene: GPR156 was added
gene: GPR156 was added to Monogenic hearing loss. Sources: Research
Mode of inheritance for gene: GPR156 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPR156 were set to PMID:36928829
Phenotypes for gene: GPR156 were set to sensorineural hearing loss
Penetrance for gene: GPR156 were set to Complete
Review for gene: GPR156 was set to GREEN
Added comment: The association between biallelic LoF variants in GPR156 and non-syndromic sensorineural hearing loss was identified in an association analysis in the 100KGP RD main programme in two pedigrees and replicated in a further large independent pedigree (reported in PMID:36928819). A causal association is supported by replication of the phenotype in a GPR156-/- mouse model and credible mechanistic evidence in primary cel cultures (PMID:34001891).
Sources: Research
Monogenic hearing loss v4.14 GOSR2 Achchuthan Shanmugasundram gene: GOSR2 was added
gene: GOSR2 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: GOSR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOSR2 were set to 37074134
Phenotypes for gene: GOSR2 were set to hearing loss, autosomal recessive, MONDO:0019588
Review for gene: GOSR2 was set to RED
Added comment: Four children from two sibships from an extended consanguineous Palestinian family were reported with congenital profound hearing loss, whereas the parents of both sibships are first cousins with normal hearing. The families reported occasional febrile seizures in infancy for each of the deaf children, but these did not persist into adolescence. These affected children were identified with autosomal recessive GOSR2 variant, c.1A > C, p.Met1Leu. This variant appeared once in the gnomAD database, as a heterozygote, and not in any of ~2000 in-house controls of Palestinian ancestry.

All previously reported cases with biallelic GOSR2 variants had normal hearing and hence the differences in translation efficiency due to the effect of this variant may be responsible for this hearing loss phenotype (PMID:37074134).
Sources: Literature
Monogenic hearing loss v4.13 LETM1 Sarah Leigh Tag Q3_23_NHS_review was removed from gene: LETM1.
Monogenic hearing loss v4.13 LETM1 Sarah Leigh Entity copied from Possible mitochondrial disorder - nuclear genes v3.42
Monogenic hearing loss v4.13 LETM1 Sarah Leigh gene: LETM1 was added
gene: LETM1 was added to Monogenic hearing loss. Sources: Expert Review,Expert Review Amber
Q3_23_promote_green, Q3_23_NHS_review, Q3_23_MOI tags were added to gene: LETM1.
Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LETM1 were set to 36055214; 33815143
Phenotypes for gene: LETM1 were set to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Monogenic hearing loss v4.12 DNAJC3 Achchuthan Shanmugasundram Classified gene: DNAJC3 as Amber List (moderate evidence)
Monogenic hearing loss v4.12 DNAJC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are seven unrelated families with DNAJC3 biallelic variants and presenting with sensorineural hearing loss. Hence, this gene can be promoted to Green at the next GMS review.
Monogenic hearing loss v4.12 DNAJC3 Achchuthan Shanmugasundram Gene: dnajc3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.11 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DNAJC3.
Monogenic hearing loss v4.11 DNAJC3 Achchuthan Shanmugasundram changed review comment from: PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)), of which all three individuals from family 1 and one of two individuals from family 2 were reported with sensorineural hearing loss among several clinical manifestations.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with sensorineural hearing loss.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorineural hearing loss.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, and both had sensorineural hearing loss.

PMID:34654017 - Ttwo siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with sensorineural hearing loss.
Sources: Literature; to: PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)), of which all three individuals from family 1 and one of two individuals from family 2 were reported with sensorineural hearing loss among several clinical manifestations.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with sensorineural hearing loss.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorineural hearing loss.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, and both had sensorineural hearing loss.

PMID:34654017 - Two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with sensorineural hearing loss.
Sources: Literature
Monogenic hearing loss v4.11 DNAJC3 Achchuthan Shanmugasundram gene: DNAJC3 was added
gene: DNAJC3 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: DNAJC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC3 were set to 25466870; 28940199; 32738013; 33486469; 34654017
Phenotypes for gene: DNAJC3 were set to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, OMIM:616192
Review for gene: DNAJC3 was set to GREEN
Added comment: PMID:25466870 - Five individuals from two different families were identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)), of which all three individuals from family 1 and one of two individuals from family 2 were reported with sensorineural hearing loss among several clinical manifestations.

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with sensorineural hearing loss.

PMID:32738013 - Two unrelated cases with homozygous splice site variants (case 1: c.393+2T>G; case 2: c.393+2T>C) in DNAJC3 and were reported with sensorineural hearing loss.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, and both had sensorineural hearing loss.

PMID:34654017 - Ttwo siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with sensorineural hearing loss.
Sources: Literature
Monogenic hearing loss v4.10 PTPRQ Achchuthan Shanmugasundram changed review comment from: PMID:29309402 - A heterozygous nonsense variant (c.6881G>A; p.Trp2294Ter) was identified in a four-generation German family with nonsyndromic mild to severe hearing loss of the mid- to high frequencies and onset from early childhood to second decade in seven members.

PMID:31655630 - The same variant (c.6881G>A; p.Trp2294Ter) was identified in a five-generation Polish family with autosomal dominant non-syndromic hearing loss (ADNSHL). Using genome-wide linkage analysis, the authors also found that the studied Polish family and the original German family derive from a common ancestor.

PMID:33229591 - PTPRQ variants p.Gly383Glu and p.Arg841Trp were identified in multiplex family age-related hearing loss (mARHL) cases, while p.Ser1022Arg, c.4286-1G>T and p.Leu879Argfs*20 were identified with simplex/sporadic age-related hearing loss (sARHL) cases. However, p.Ser321Cys was identified in control cases with normal hearing.; to: PMID:29309402 - A heterozygous nonsense variant (c.6881G>A; p.Trp2294Ter) was identified in a four-generation German family with nonsyndromic mild to severe hearing loss of the mid- to high frequencies and onset from early childhood to second decade in seven members.

PMID:31655630 - The same variant (c.6881G>A; p.Trp2294Ter) was identified in a five-generation Polish family with autosomal dominant non-syndromic hearing loss (ADNSHL). Using genome-wide linkage analysis, the authors also found that the studied Polish family and the original German family derive from a common ancestor.

PMID:33229591 - PTPRQ variants p.Gly383Glu and p.Arg841Trp were identified in multiplex family age-related hearing loss (mARHL) cases, while p.Ser1022Arg, c.4286-1G>T and p.Leu879Argfs*20 were identified with simplex/sporadic age-related hearing loss (sARHL) cases. However, p.Ser321Cys was identified in control cases with normal hearing.

This gene has been associated with hearing loss caused by both autosomal dominant (MIM #617663) and autosomal recessive (MIM #613391) inheritance in OMIM.
Monogenic hearing loss v4.10 PTPRQ Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As there are sufficient cases/ variants reported with monoallelic inheritance and hearing loss, the MOI should be changed from "BIALLELIC, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next major review.
Monogenic hearing loss v4.10 PTPRQ Achchuthan Shanmugasundram Mode of inheritance for gene: PTPRQ was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.9 PTPRQ Achchuthan Shanmugasundram Tag Q3_23_MOI tag was added to gene: PTPRQ.
Monogenic hearing loss v4.9 PTPRQ Achchuthan Shanmugasundram reviewed gene: PTPRQ: Rating: GREEN; Mode of pathogenicity: None; Publications: 29309402, 31655630, 33229591; Phenotypes: Deafness, autosomal dominant 73, OMIM:617663, Deafness, autosomal recessive 84A, OMIM:613391; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v4.9 ATP2B2 Eleanor Williams Classified gene: ATP2B2 as Amber List (moderate evidence)
Monogenic hearing loss v4.9 ATP2B2 Eleanor Williams Added comment: Comment on list classification: There is now enough evidence to show that variants in this gene can cause hearing loss so the recommendation is that this gene is rated Green following GMS review.
Monogenic hearing loss v4.9 ATP2B2 Eleanor Williams Gene: atp2b2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.8 ATP2B2 Eleanor Williams Phenotypes for gene: ATP2B2 were changed from {Deafness, autosomal recessive 12, modifier of} 601386 to {Deafness, autosomal recessive 12, modifier of}, OMIM:601386; Deafness, autosomal dominant 82, OMIM:619804; hearing loss, autosomal dominant 82, MONDO:0030719
Monogenic hearing loss v4.7 ATP2B2 Eleanor Williams Publications for gene: ATP2B2 were set to 30535804; 17234811
Monogenic hearing loss v4.6 ATP2B2 Eleanor Williams Tag Q2_23_promote_green tag was added to gene: ATP2B2.
Tag Q2_23_NHS_review tag was added to gene: ATP2B2.
Monogenic hearing loss v4.6 ATP2B2 Eleanor Williams changed review comment from: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on HI, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.; to: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on Hearing impairment, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.
Monogenic hearing loss v4.6 LMX1A Achchuthan Shanmugasundram Publications for gene: LMX1A were set to 29754270; 29971487; 32840933; 19540218; 18985389
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Classified gene: STX4 as Amber List (moderate evidence)
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as it has been implicated in congenital hearing impairment, as identified from one family and supported by functional studies.
Monogenic hearing loss v4.5 STX4 Achchuthan Shanmugasundram Gene: stx4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.4 STX4 Achchuthan Shanmugasundram gene: STX4 was added
gene: STX4 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: STX4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX4 were set to 36355422
Phenotypes for gene: STX4 were set to Hearing impairment, HP:0000365
Review for gene: STX4 was set to AMBER
Added comment: PMID:36355422 reported a large consanguineous Pakistani family with eight affected individuals showing bilateral severe-to-profound hearing impairment. A homozygous splice region variant was identified in STX4 (c.232 + 6T>C), which causes exon skipping and a frameshift, that segregated with hearing impairment in this family.

In silico analysis showed that murine Stx4a is highly and widespread expressed in the developing and adult inner ear. Knockdown of stx4 in zebrafish showed an abnormal startle response, morphological and developmental defects, and a disrupted mechanotransduction function in neuromast hair cells.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Classified gene: ATP11A as Amber List (moderate evidence)
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as it has been implicated in sensorineural hearing loss from four unrelated families, and supported by functional studies from mouse model.
Monogenic hearing loss v4.3 ATP11A Achchuthan Shanmugasundram Gene: atp11a has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.2 ATP11A Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: ATP11A.
Monogenic hearing loss v4.2 ATP11A Achchuthan Shanmugasundram gene: ATP11A was added
gene: ATP11A was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP11A were set to 35278131; 36300302
Phenotypes for gene: ATP11A were set to Deafness, autosomal dominant 84, OMIM:619810
Review for gene: ATP11A was set to GREEN
Added comment: A heterozygous cryptic donor splice site variant in ATP11A has been identified in a large 6-generation family from Newfoundland in which 16 individuals had progressive sensorineural hearing loss. In addition, several individuals with postlingual-onset progressive hearing loss from two unrelated multigenerational Jewish Israeli families with their origins in Uzbekistan and Afghanistan were also identified with a novel duplication in ATP11A (PMID:35278131).

5500 bp deletion involving the last coding exon of both ATP11A isoforms were identified in the large German multi-generational family that was first reported in PMID:28601886 with auditory synaptopathy/neuropathy, which is a distinct type of sensorineural hearing loss. The deletion is present in all affected individuals from the family and absent in two unaffected family members tested (PMID:36300302).

Functional studies in mice showed ATP11A protein is expressed in mouse inner ear and conditional Atp11a knockout mice showed age-progressive dysfunction or loss of spiral ganglion neurons, recapitulating the human phenotype of auditory neuropathy (PMID:36300302).

This gene has been associated with relevant phenotypes in OMIM, but not in Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Monogenic hearing loss v4.0 Arina Puzriakova promoted panel to version 4.0
Monogenic hearing loss v3.17 Arina Puzriakova Panel signed off version 3.15 has been removed
Monogenic hearing loss v3.16 Arina Puzriakova Panel version 3.15 has been signed off on 2023-03-22
Monogenic hearing loss v3.15 Arina Puzriakova Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Monogenic hearing loss v3.14 ATP2B2 Claire Walder reviewed gene: ATP2B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30535804, 33111345, 33105617; Phenotypes: Deafness, autosomal dominant 82; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v3.14 EPHA10 Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. Particularly, Eph overexpressed flies had a poorer performance compared to controls in negative geotaxis assay. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. Particularly, Eph overexpressed flies had a poorer performance compared to controls in negative geotaxis assay. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v3.14 EPHA10 Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. Particularly, Eph overexpressed flies had a poorer performance compared to controls in negative geotaxis assay. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v3.14 OXR1 Achchuthan Shanmugasundram changed review comment from: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.
Sources: Literature; to: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.

This gene has not yet been associated with hearing loss either in OMIM or in Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v3.14 OXR1 Achchuthan Shanmugasundram changed review comment from: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.
Sources: Literature; to: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.
Sources: Literature
Monogenic hearing loss v3.14 OXR1 Achchuthan Shanmugasundram Classified gene: OXR1 as Amber List (moderate evidence)
Monogenic hearing loss v3.14 OXR1 Achchuthan Shanmugasundram Gene: oxr1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v3.13 OXR1 Achchuthan Shanmugasundram gene: OXR1 was added
gene: OXR1 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXR1 were set to 36130215
Phenotypes for gene: OXR1 were set to sensorineural hearing loss disorder, MONDO:0020678
Review for gene: OXR1 was set to AMBER
Added comment: Comment on gene rating: This gene should be rated AMBER as there is one case and supportive functional data to associate OXR1 with hearing loss.

A four years old girl was identified with a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in OXR1 gene and was reported with sensorineural hearing loss.

Functional studies in zebrafish model showed that the ortholog orx1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL). In addition, knockdown of oxr1b resulted in a significant developmental defect of SAG and pLL and this phenotype was rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs.
Sources: Literature
Monogenic hearing loss v3.12 EPHA10 Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model.
Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model. These functional evidence suggests that 'gain of function' may be responsible for the hearing loss phenotype.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Sources: Literature
Monogenic hearing loss v3.12 EPHA10 Achchuthan Shanmugasundram edited their review of gene: EPHA10: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Monogenic hearing loss v3.12 EPHA10 Achchuthan Shanmugasundram changed review comment from: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected unregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model.
Sources: Literature; to: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected upregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model.
Sources: Literature
Monogenic hearing loss v3.12 EPHA10 Achchuthan Shanmugasundram gene: EPHA10 was added
gene: EPHA10 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: EPHA10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHA10 were set to 36048850
Phenotypes for gene: EPHA10 were set to postlingual non-syndromic genetic hearing loss, MONDO:0016298
Review for gene: EPHA10 was set to RED
Added comment: Comment on rating: This gene should be rated RED as this gene has been associated with post-lingual autosomal dominant non-syndromic hearing loss from a single family, and supported by functional studies.

PMID:36048850 reported the identification of a heterozygous non-coding variant c.-81_-73delinsAGC cosegregating with hearing loss. Although variants have been identified in KIF17 and USP48 in several members of this family, they did not cosegregate with hearing loss. One affected member of this family had an ideal hearing restoration after cochlear implantation.

Epha10 was expressed in mouse cochlea at both transcription and translation levels. In addition, EPHA10 mRNA was detected unregulated in patients compared with controls by qRT-PCR. Overexpression of Eph (the homolog of human EPHA10) altered the structure and function of chordotonal organ (equivalent to mammalian auditory organs) in fly model.
Sources: Literature
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated GREEN as it has been associated with auditory neuropathy in two unrelated cases with homozygous variant and with sensorineural hearing loss in an additional case with compound heterozygous variant.; to: Comment on list classification: This gene should be rated GREEN as it has been associated with auditory neuropathy in two unrelated cases with homozygous variant and with sensorineural hearing loss in an additional case with compound heterozygous variant. This is also supported by functional studies.
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CRLS1.
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as it has been associated with auditory neuropathy in two unrelated cases with homozygous variant and with sensorineural hearing loss in an additional case with compound heterozygous variant.
Monogenic hearing loss v3.11 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v3.10 CRLS1 Achchuthan Shanmugasundram Publications for gene: CRLS1 were set to 5147173
Monogenic hearing loss v3.9 CRLS1 Achchuthan Shanmugasundram edited their review of gene: CRLS1: Changed publications to: 35147173
Monogenic hearing loss v3.9 CRLS1 Achchuthan Shanmugasundram gene: CRLS1 was added
gene: CRLS1 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 5147173
Phenotypes for gene: CRLS1 were set to Combined oxidative phosphorylation deficiency 57, OMIM:620167
Review for gene: CRLS1 was set to GREEN
Added comment: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Functional studies using patient-derived fibroblasts provide evidence that CRLS1 variants cause mitochondrial disease.
Sources: Literature
Monogenic hearing loss v3.8 SPATA5L1 Eleanor Williams Tag gene-checked tag was added to gene: SPATA5L1.
Monogenic hearing loss v3.8 DVL2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DVL2.
Monogenic hearing loss v3.8 ISCA-46297-Loss Arina Puzriakova edited their review of Region: ISCA-46297-Loss: Changed rating: GREEN
Monogenic hearing loss v3.8 ISCA-46297-Loss Arina Puzriakova commented on Region: ISCA-46297-Loss
Monogenic hearing loss v3.8 ISCA-46297-Loss Arina Puzriakova Region: ISCA-46297-Loss was added
Region: ISCA-46297-Loss was added to Monogenic hearing loss. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46297-Loss was set to BIALLELIC, autosomal or pseudoautosomal
Publications for Region: ISCA-46297-Loss were set to 31204719; 19888295; 20301607; 25719193; 30836598
Monogenic hearing loss v3.7 FOXI1 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: FOXI1.
Monogenic hearing loss v3.7 COL9A3 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: COL9A3.
Monogenic hearing loss v3.7 USP48 Arina Puzriakova Tag Q4_21_rating was removed from gene: USP48.
Monogenic hearing loss v3.7 SPATA5L1 Arina Puzriakova Tag Q1_22_rating was removed from gene: SPATA5L1.
Monogenic hearing loss v3.7 RNF220 Arina Puzriakova Tag Q4_21_rating was removed from gene: RNF220.
Monogenic hearing loss v3.7 PBX1 Arina Puzriakova Tag Q4_21_rating was removed from gene: PBX1.
Monogenic hearing loss v3.7 OGDHL Arina Puzriakova Tag Q3_22_rating was removed from gene: OGDHL.
Monogenic hearing loss v3.7 LMX1A Arina Puzriakova Tag Q1_22_MOI was removed from gene: LMX1A.
Monogenic hearing loss v3.7 KCNJ16 Arina Puzriakova Tag Q2_22_rating was removed from gene: KCNJ16.
Monogenic hearing loss v3.7 GREB1L Arina Puzriakova Tag Q2_21_rating was removed from gene: GREB1L.
Monogenic hearing loss v3.7 GGPS1 Arina Puzriakova Tag Q4_21_rating was removed from gene: GGPS1.
Monogenic hearing loss v3.7 CRYM Arina Puzriakova Tag Q2_21_rating was removed from gene: CRYM.
Monogenic hearing loss v3.7 CLDN9 Arina Puzriakova Tag Q4_21_rating was removed from gene: CLDN9.
Monogenic hearing loss v3.7 CEACAM16 Arina Puzriakova Tag Q4_21_MOI was removed from gene: CEACAM16.
Monogenic hearing loss v3.7 AP1S1 Arina Puzriakova Tag Q2_21_rating was removed from gene: AP1S1.
Monogenic hearing loss v3.7 ADGRV1 Arina Puzriakova Tag Q1_22_MOI was removed from gene: ADGRV1.
Monogenic hearing loss v3.7 FOXI1 Arina Puzriakova commented on gene: FOXI1
Monogenic hearing loss v3.7 COL9A3 Arina Puzriakova commented on gene: COL9A3
Monogenic hearing loss v3.7 USP48 Arina Puzriakova reviewed gene: USP48: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 SPATA5L1 Arina Puzriakova reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 RNF220 Arina Puzriakova reviewed gene: RNF220: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 PBX1 Arina Puzriakova reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 OGDHL Arina Puzriakova edited their review of gene: OGDHL: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Monogenic hearing loss v3.7 LMX1A Arina Puzriakova commented on gene: LMX1A
Monogenic hearing loss v3.7 KCNJ16 Arina Puzriakova reviewed gene: KCNJ16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 GREB1L Arina Puzriakova reviewed gene: GREB1L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 GGPS1 Arina Puzriakova reviewed gene: GGPS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 CRYM Arina Puzriakova reviewed gene: CRYM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 CLDN9 Arina Puzriakova reviewed gene: CLDN9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 CEACAM16 Arina Puzriakova commented on gene: CEACAM16
Monogenic hearing loss v3.7 AP1S1 Arina Puzriakova reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 ADGRV1 Arina Puzriakova commented on gene: ADGRV1
Monogenic hearing loss v3.6 USP48 Arina Puzriakova Source NHS GMS was added to USP48.
Source Expert Review Green was added to USP48.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 SPATA5L1 Arina Puzriakova Source NHS GMS was added to SPATA5L1.
Source Expert Review Green was added to SPATA5L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 RNF220 Arina Puzriakova Source NHS GMS was added to RNF220.
Source Expert Review Green was added to RNF220.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 PBX1 Arina Puzriakova Source NHS GMS was added to PBX1.
Source Expert Review Green was added to PBX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 OGDHL Arina Puzriakova Source NHS GMS was added to OGDHL.
Source Expert Review Green was added to OGDHL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 LMX1A Arina Puzriakova Source NHS GMS was added to LMX1A.
Mode of inheritance for gene LMX1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v3.6 KCNJ16 Arina Puzriakova Source NHS GMS was added to KCNJ16.
Source Expert Review Green was added to KCNJ16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 GREB1L Arina Puzriakova Source NHS GMS was added to GREB1L.
Source Expert Review Green was added to GREB1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 GGPS1 Arina Puzriakova Source NHS GMS was added to GGPS1.
Source Expert Review Green was added to GGPS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 CRYM Arina Puzriakova Source NHS GMS was added to CRYM.
Source Expert Review Green was added to CRYM.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 CLDN9 Arina Puzriakova Source NHS GMS was added to CLDN9.
Source Expert Review Green was added to CLDN9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 CEACAM16 Arina Puzriakova Source NHS GMS was added to CEACAM16.
Mode of inheritance for gene CEACAM16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v3.6 AP1S1 Arina Puzriakova Source NHS GMS was added to AP1S1.
Source Expert Review Green was added to AP1S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 ADGRV1 Arina Puzriakova Source NHS GMS was added to ADGRV1.
Mode of inheritance for gene ADGRV1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v3.5 ACOX1 Mafalda Gomes reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32169171; Phenotypes: Mitchell syndrome, OMIM:618960; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v3.4 ACOX1 Mafalda Gomes gene: ACOX1 was added
gene: ACOX1 was added to Monogenic hearing loss. Sources: Expert Review Amber
Mode of inheritance for gene: ACOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v3.3 SLC52A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, OMIM:614707 to Brown-Vialetto-Van Laere syndrome 2, OMIM:614707, MONDO:0013867; Sensorineural hearing loss disorder, MONDO:0020678
Monogenic hearing loss v3.2 SLC52A2 Achchuthan Shanmugasundram Publications for gene: SLC52A2 were set to 22740598; 22864630; 23243084; 24253200
Monogenic hearing loss v3.1 SLC52A2 Achchuthan Shanmugasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 22864630, 23243084, 24253200, 30343981, 30377535, 31868069, 35608644, 36186484; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867, Sensorineural hearing loss disorder, MONDO:0020678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Monogenic hearing loss v3.0 Arina Puzriakova promoted panel to version 3.0
Monogenic hearing loss v2.249 Arina Puzriakova Panel name changed from Hearing loss to Monogenic hearing loss
List of related panels changed from Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe); R67 to Hearing loss; Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe); Non-syndromic hearing loss; R67
Monogenic hearing loss v2.248 FOXI1 Eleanor Williams Tag Q1_22_expert_review tag was added to gene: FOXI1.
Monogenic hearing loss v2.248 COL9A3 Eleanor Williams Tag Q2_21_rating tag was added to gene: COL9A3.
Tag Q2_21_expert_review tag was added to gene: COL9A3.
Monogenic hearing loss v2.248 KDM3B Sarah Leigh Phenotypes for gene: KDM3B were changed from Global developmental delay; Intellectual disability; Short stature; Behavioral abnormality; Seizures to Diets-Jongmans syndrome, OMIM:618846; Diets-Jongmans syndrome, MONDO:0030012
Monogenic hearing loss v2.247 PTPRQ Barbara Vona reviewed gene: PTPRQ: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29309402, PMID: 31655630; Phenotypes: DEAFNESS, AUTOSOMAL DOMINANT 73, DFNA73; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Monogenic hearing loss v2.247 GRAP Barbara Vona gene: GRAP was added
gene: GRAP was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: GRAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRAP were set to PMID: 30610177
Phenotypes for gene: GRAP were set to Non-syndromic hearing loss
Penetrance for gene: GRAP were set to Complete
Review for gene: GRAP was set to RED
Added comment: Two consanguineous families were identified with the same c.311A>T, p.(Gln104Leu) homozygous variant in GRAP. The affected individuals in both families reported congenital profound sensorineural hearing loss. GRAP is expressed in the mouse inner ear in the neuronal fibers innervating cochlear and utricular auditory hair cells. In the fly, it is expressed in the hearing organ, called the Johnston's organ, in cells that include the mechanosensory neurons. Transgenic flies with the human variant showed loss of protein function in vivo. This gene has been assigned to the DFNB114 locus in OMIM (OMIM: #618456).
Sources: Literature
Monogenic hearing loss v2.247 OGDHL Arina Puzriakova Entity copied from Intellectual disability v3.1644
Monogenic hearing loss v2.247 OGDHL Arina Puzriakova gene: OGDHL was added
gene: OGDHL was added to Hearing loss. Sources: Expert Review Amber,Literature
Q3_22_rating tags were added to gene: OGDHL.
Mode of inheritance for gene: OGDHL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGDHL were set to 28017472; 34800363
Phenotypes for gene: OGDHL were set to Yoon-Bellen neurodevelopmental syndrome, OMIM:619701
Monogenic hearing loss v2.246 GSTT1 Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: GSTT1.
Monogenic hearing loss v2.246 GSTT1 Eleanor Williams commented on gene: GSTT1
Monogenic hearing loss v2.246 KCNJ16 Eleanor Williams Tag watchlist was removed from gene: KCNJ16.
Tag Q2_22_rating tag was added to gene: KCNJ16.
Monogenic hearing loss v2.246 KCNJ16 Eleanor Williams changed review comment from: Comment on list classification: Rating this gene as amber, 7 cases reported in PMID:33811157 but details of the nature of the hearing loss could not be obtained due to inaccessibility of the publication.; to: Comment on list classification: Rating this gene as amber, but with a recommendation of green rating following GMS review. 7 families reported in PMID:33811157 with hearing loss developing in affected individuals in childhood or adolescence.
Monogenic hearing loss v2.246 KCNJ16 Eleanor Williams changed review comment from: Associated with Hypokalemic tubulopathy and deafness OMIM#619406 (AR)

PMID:33811157 - Schlingmann et al 2021 - unable to access publication. Abstract does not give numbers of cases but OMIM states that "In 8 patients, including 1 sib pair, with hypokalemic tubulopathy and deafness, Schlingmann et al. (2021) identified homozygous or compound heterozygous mutations in the KCNJ16 gene". Details of the hearing loss could not be acertained.

PMID:33840812 - Webb et al 2021 - report a homozygous loss-of-function variant identified by WES in KCNJ16 in a 2-year-old female with a hypokalemic metabolic acidosis phenotype. Hearing loss is NOT mentioned.
Sources: Literature; to: Associated with Hypokalemic tubulopathy and deafness OMIM#619406 (AR)

PMID:33811157 - Schlingmann et al 2021 - report 8 patients from 7 families with hypokalemic tubulopathy and deafness. All patients had acidosis and sensorineural deafness. Hearing loss was diagnosed in childhood or adolescence. All were found to have homozygous or compound heterozygous variants in the KCNJ16 gene. 6 different variants were identified, either missense or nonsesnse. Functional studies showed that variants affect the function of heteromeric potassium channels.

PMID:33840812 - Webb et al 2021 - report a homozygous loss-of-function variant identified by WES in KCNJ16 in a 2-year-old female with a hypokalemic metabolic acidosis phenotype. Hearing loss is NOT mentioned.
Sources: Literature
Monogenic hearing loss v2.246 KCNJ16 Eleanor Williams changed review comment from: Comment on list classification: Rating this gene as amber, 7 cases reported in PMID:33811157 but details of how many had hearing loss or the details of the nature of the hearing loss could not be obtained due to inaccessibility of the publication.; to: Comment on list classification: Rating this gene as amber, 7 cases reported in PMID:33811157 but details of the nature of the hearing loss could not be obtained due to inaccessibility of the publication.
Monogenic hearing loss v2.246 KCNJ16 Eleanor Williams Classified gene: KCNJ16 as Amber List (moderate evidence)
Monogenic hearing loss v2.246 KCNJ16 Eleanor Williams Added comment: Comment on list classification: Rating this gene as amber, 7 cases reported in PMID:33811157 but details of how many had hearing loss or the details of the nature of the hearing loss could not be obtained due to inaccessibility of the publication.
Monogenic hearing loss v2.246 KCNJ16 Eleanor Williams Gene: kcnj16 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.245 KCNJ16 Eleanor Williams gene: KCNJ16 was added
gene: KCNJ16 was added to Hearing loss. Sources: Literature
watchlist tags were added to gene: KCNJ16.
Mode of inheritance for gene: KCNJ16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNJ16 were set to 33811157; 33840812
Phenotypes for gene: KCNJ16 were set to Hypokalemic tubulopathy and deafness, OMIM:619406
Review for gene: KCNJ16 was set to AMBER
Added comment: Associated with Hypokalemic tubulopathy and deafness OMIM#619406 (AR)

PMID:33811157 - Schlingmann et al 2021 - unable to access publication. Abstract does not give numbers of cases but OMIM states that "In 8 patients, including 1 sib pair, with hypokalemic tubulopathy and deafness, Schlingmann et al. (2021) identified homozygous or compound heterozygous mutations in the KCNJ16 gene". Details of the hearing loss could not be acertained.

PMID:33840812 - Webb et al 2021 - report a homozygous loss-of-function variant identified by WES in KCNJ16 in a 2-year-old female with a hypokalemic metabolic acidosis phenotype. Hearing loss is NOT mentioned.
Sources: Literature
Monogenic hearing loss v2.244 SLITRK6 Arina Puzriakova Mode of inheritance for gene: SLITRK6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.243 CISD2 Arina Puzriakova Mode of inheritance for gene: CISD2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.242 MT-TS1 Eleanor Williams Tag gene-checked tag was added to gene: MT-TS1.
Monogenic hearing loss v2.242 GREB1L Eleanor Williams Tag gene-checked tag was added to gene: GREB1L.
Monogenic hearing loss v2.242 MT-RNR1 Arina Puzriakova Tag gene-checked tag was added to gene: MT-RNR1.
Monogenic hearing loss v2.242 OPA1 Arina Puzriakova Phenotypes for gene: OPA1 were changed from #125250:Optic atrophy plus syndrome; #165500:Optic atrophy 1; #606657:{Glaucoma, normal tension, susceptibility to} to Optic atrophy 1, OMIM:165500; Optic atrophy plus syndrome, OMIM:125250
Monogenic hearing loss v2.241 MYO7A Arina Puzriakova Phenotypes for gene: MYO7A were changed from hearing loss; Usher syndrome, type 1B, 276900; Nonsyndromic Hearing Loss, Dominant; #600060:Deafness, autosomal recessive 2; Nonsyndromic Hearing Loss, Recessive; #601317:Deafness, autosomal dominant 11 to Deafness, autosomal dominant 11, OMIM:601317; Deafness, autosomal recessive 2, OMIM:600060; Usher syndrome, type 1B, OMIM:276900
Monogenic hearing loss v2.240 KCNQ4 Arina Puzriakova Phenotypes for gene: KCNQ4 were changed from #600101:Deafness, autosomal dominant 2A to Deafness, autosomal dominant 2A, OMIM:600101
Monogenic hearing loss v2.239 GRHL2 Arina Puzriakova Phenotypes for gene: GRHL2 were changed from hearing loss; Deafness, autosomal dominant 28, 608641; #616029: Ectodermal dysplasia/short stature syndrome to Deafness, autosomal dominant 28, OMIM:608641; Ectodermal dysplasia/short stature syndrome, OMIM:616029
Monogenic hearing loss v2.238 PNPT1 Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13, 614932; Deafness, autosomal recessive 70, 614934 to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Deafness, autosomal recessive 70, OMIM:614934
Monogenic hearing loss v2.237 COL9A3 Eleanor Williams Tag for-review was removed from gene: COL9A3.
Monogenic hearing loss v2.237 DMXL2 Eleanor Williams Tag for-review was removed from gene: DMXL2.
Monogenic hearing loss v2.237 COL9A2 Eleanor Williams Tag for-review was removed from gene: COL9A2.
Monogenic hearing loss v2.237 FOXI1 Eleanor Williams Tag Q1_22_MOI tag was added to gene: FOXI1.
Monogenic hearing loss v2.237 NARS2 Eleanor Williams Tag for-review was removed from gene: NARS2.
Monogenic hearing loss v2.237 MORC2 Eleanor Williams Tag for-review was removed from gene: MORC2.
Monogenic hearing loss v2.237 COG4 Eleanor Williams Tag for-review was removed from gene: COG4.
Monogenic hearing loss v2.237 SNAI2 Eleanor Williams Phenotypes for gene: SNAI2 were changed from Waardenburg syndrome, type 2D, 608890; Piebaldism, 172800 to Waardenburg syndrome, type 2D, OMIM:608890; Waardenburg syndrome type 2, MONDO_0019517
Monogenic hearing loss v2.236 SNAI2 Eleanor Williams Tag for-review was removed from gene: SNAI2.
Monogenic hearing loss v2.236 SLITRK6 Eleanor Williams Phenotypes for gene: SLITRK6 were changed from Deafness and myopia, 221200; high myopia-sensorineural deafness syndrome MONDO:0009082 to Deafness and myopia, OMIM:221200; high myopia-sensorineural deafness syndrome MONDO:0009082
Monogenic hearing loss v2.235 SLITRK6 Eleanor Williams Tag for-review was removed from gene: SLITRK6.
Monogenic hearing loss v2.235 SLC52A3 Eleanor Williams Phenotypes for gene: SLC52A3 were changed from Brown-Vialetto-Van Laere syndrome 1 #211530 to Brown-Vialetto-Van Laere syndrome 1, OMIM:211530
Monogenic hearing loss v2.234 SLC52A3 Eleanor Williams Tag for-review was removed from gene: SLC52A3.
Monogenic hearing loss v2.234 SLC52A2 Eleanor Williams Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2 #614707 to Brown-Vialetto-Van Laere syndrome 2, OMIM:614707
Monogenic hearing loss v2.233 SLC52A2 Eleanor Williams Tag for-review was removed from gene: SLC52A2.
Monogenic hearing loss v2.233 SLC12A2 Eleanor Williams Tag for-review was removed from gene: SLC12A2.
Monogenic hearing loss v2.233 RIPOR2 Eleanor Williams Phenotypes for gene: RIPOR2 were changed from Hearing loss, non-syndromic, autosomal recessive (Diaz-Horta (2014) Proc Natl AcadSci USA 111,9864); Sensorineural hearing loss; OrphaNet: ORPHA90636; OMIM:616515 to ?Deafness, autosomal recessive 104 , OMIM:616515
Monogenic hearing loss v2.232 PLS1 Eleanor Williams Phenotypes for gene: PLS1 were changed from Deafness, autosomal dominant 76 OMIM:618787; deafness, autosomal dominant 76 MONDO:0032917 to Deafness, autosomal dominant 76, OMIM:618787; deafness, autosomal dominant 76, MONDO:0032917
Monogenic hearing loss v2.231 PLS1 Eleanor Williams Tag for-review was removed from gene: PLS1.
Monogenic hearing loss v2.231 MPZL2 Eleanor Williams Phenotypes for gene: MPZL2 were changed from Deafness, autosomal recessive 111 OMIM:618145; deafness, autosomal recessive 111 MONDO:0029142 to Deafness, autosomal recessive 111, OMIM:618145; deafness, autosomal recessive 111, MONDO:0029142
Monogenic hearing loss v2.230 MPZL2 Eleanor Williams Tag for-review was removed from gene: MPZL2.
Monogenic hearing loss v2.230 MN1 Eleanor Williams Tag for-review was removed from gene: MN1.
Monogenic hearing loss v2.230 LMX1A Eleanor Williams commented on gene: LMX1A: The MOI of this gene should be reviewed at the next update to consider whether it should be set to Both mono and bi-allelic
Monogenic hearing loss v2.230 LMX1A Eleanor Williams Tag Q1_22_MOI tag was added to gene: LMX1A.
Monogenic hearing loss v2.230 LMX1A Eleanor Williams changed review comment from: Comment on mode of inheritance: Setting MOI to Monoallelic as only one case of biallelic reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.; to: Comment on mode of inheritance: Setting MOI to Monoallelic as only one case of biallelic reported to date
Monogenic hearing loss v2.230 LMX1A Eleanor Williams Tag watchlist was removed from gene: LMX1A.
Tag for-review was removed from gene: LMX1A.
Monogenic hearing loss v2.230 HARS2 Eleanor Williams Tag for-review was removed from gene: HARS2.
Monogenic hearing loss v2.230 FOXI1 Eleanor Williams Tag for-review was removed from gene: FOXI1.
Monogenic hearing loss v2.230 FDXR Eleanor Williams Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Auditory neuropathy and optic atrophy, OMIM:617717
Monogenic hearing loss v2.229 FDXR Eleanor Williams Tag for-review was removed from gene: FDXR.
Monogenic hearing loss v2.229 EPS8L2 Eleanor Williams Phenotypes for gene: EPS8L2 were changed from Deafness, autosomal recessive 106, MIM#617637 to Deafness, autosomal recessive 106, OMIM:617637
Monogenic hearing loss v2.228 EPS8L2 Eleanor Williams Tag for-review was removed from gene: EPS8L2.
Monogenic hearing loss v2.228 DMXL2 Eleanor Williams Phenotypes for gene: DMXL2 were changed from ?Deafness, autosomal dominant 71, 617605; Epileptic encephalopathy, early infantile, 81, 618663 to ?Deafness, autosomal dominant 71, OMIM:617605
Monogenic hearing loss v2.227 COL9A1 Eleanor Williams Tag for-review was removed from gene: COL9A1.
Monogenic hearing loss v2.227 COL4A6 Eleanor Williams Tag for-review was removed from gene: COL4A6.
Monogenic hearing loss v2.227 COL4A6 Eleanor Williams Phenotypes for gene: COL4A6 were changed from #300914:?Deafness, X-linked 6; diffuse leiomyomatosis with Alport syndrome = contiguous gene with COL4A5; Leiomyomatosis, diffuse, with Alport syndrome, 308940 (4) to Deafness, X-linked 6, OMIM:300914
Monogenic hearing loss v2.226 COL2A1 Eleanor Williams Phenotypes for gene: COL2A1 were changed from Stickler syndrome, type I, 108300 to Stickler syndrome, type I, OMIM:108300
Monogenic hearing loss v2.225 COL2A1 Eleanor Williams Tag for-review was removed from gene: COL2A1.
Monogenic hearing loss v2.225 COL11A1 Eleanor Williams Tag for-review was removed from gene: COL11A1.
Monogenic hearing loss v2.225 COCH Eleanor Williams Tag for-review was removed from gene: COCH.
Monogenic hearing loss v2.225 CISD2 Eleanor Williams Phenotypes for gene: CISD2 were changed from hearing loss; Wolfram syndrome 2 604928 to hearing loss; Wolfram syndrome 2, OMIM:604928
Monogenic hearing loss v2.224 CISD2 Eleanor Williams Tag for-review was removed from gene: CISD2.
Monogenic hearing loss v2.224 CEP250 Eleanor Williams Tag for-review was removed from gene: CEP250.
Monogenic hearing loss v2.224 CDC14A Eleanor Williams Phenotypes for gene: CDC14A were changed from Deafness, autosomal recessive 32, with or without immotile sperm, MIM#608653 to Deafness, autosomal recessive 32, with or without immotile sperm, OMIM:608653
Monogenic hearing loss v2.223 CDC14A Eleanor Williams Tag for-review was removed from gene: CDC14A.
Monogenic hearing loss v2.223 ATP6V1B2 Eleanor Williams Tag for-review was removed from gene: ATP6V1B2.
Monogenic hearing loss v2.223 ATP6V1B2 Eleanor Williams Phenotypes for gene: ATP6V1B2 were changed from Deafness, congenital, with onychodystrophy, autosomal dominant, 124480; Zimmermann-Laband syndrome 2, 616455 to Deafness, congenital, with onychodystrophy, autosomal dominant, OMIM:124480; Zimmermann-Laband syndrome 2, OMIM:616455
Monogenic hearing loss v2.222 AIFM1 Eleanor Williams Phenotypes for gene: AIFM1 were changed from Deafness, X-linked 5, MIM#300614 to Deafness, X-linked 5, OMIM:300614
Monogenic hearing loss v2.221 AIFM1 Eleanor Williams Tag for-review was removed from gene: AIFM1.
Monogenic hearing loss v2.221 SNAI2 Eleanor Williams commented on gene: SNAI2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 SLITRK6 Eleanor Williams commented on gene: SLITRK6: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 SLC52A3 Eleanor Williams commented on gene: SLC52A3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 SLC52A2 Eleanor Williams commented on gene: SLC52A2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 SLC12A2 Eleanor Williams commented on gene: SLC12A2
Monogenic hearing loss v2.221 RIPOR2 Eleanor Williams commented on gene: RIPOR2
Monogenic hearing loss v2.221 PLS1 Eleanor Williams commented on gene: PLS1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 MPZL2 Eleanor Williams commented on gene: MPZL2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 MN1 Eleanor Williams commented on gene: MN1
Monogenic hearing loss v2.221 LMX1A Eleanor Williams commented on gene: LMX1A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 HARS2 Eleanor Williams commented on gene: HARS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 FOXI1 Eleanor Williams commented on gene: FOXI1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 FDXR Eleanor Williams commented on gene: FDXR: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 EPS8L2 Eleanor Williams commented on gene: EPS8L2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 DMXL2 Eleanor Williams commented on gene: DMXL2: The rating and mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 COL9A2 Eleanor Williams commented on gene: COL9A2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 COL9A1 Eleanor Williams commented on gene: COL9A1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 COL4A6 Eleanor Williams commented on gene: COL4A6: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 COL2A1 Eleanor Williams commented on gene: COL2A1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 COL11A1 Eleanor Williams commented on gene: COL11A1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 COCH Eleanor Williams commented on gene: COCH: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 CISD2 Eleanor Williams commented on gene: CISD2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 CEP250 Eleanor Williams commented on gene: CEP250
Monogenic hearing loss v2.221 CDC14A Eleanor Williams commented on gene: CDC14A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 ATP6V1B2 Eleanor Williams commented on gene: ATP6V1B2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 AIFM1 Eleanor Williams commented on gene: AIFM1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Monogenic hearing loss v2.221 NARS2 Eleanor Williams commented on gene: NARS2: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. The decision was too keep an Amber rating for now.
Monogenic hearing loss v2.221 MORC2 Eleanor Williams commented on gene: MORC2
Monogenic hearing loss v2.221 COG4 Eleanor Williams commented on gene: COG4
Monogenic hearing loss v2.220 SNAI2 Eleanor Williams Source Expert Review Amber was added to SNAI2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Monogenic hearing loss v2.220 SLITRK6 Eleanor Williams Source Expert Review Green was added to SLITRK6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 SLC52A3 Eleanor Williams Source Expert Review Green was added to SLC52A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 SLC52A2 Eleanor Williams Source Expert Review Green was added to SLC52A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 SLC12A2 Eleanor Williams Source Expert Review Green was added to SLC12A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 RIPOR2 Eleanor Williams Source Expert list was added to RIPOR2.
Monogenic hearing loss v2.220 PLS1 Eleanor Williams Source Expert Review Green was added to PLS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 MPZL2 Eleanor Williams Source Expert Review Green was added to MPZL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 MN1 Eleanor Williams Source Expert Review Green was added to MN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 LMX1A Eleanor Williams Source Expert Review Green was added to LMX1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 HARS2 Eleanor Williams Source Expert Review Green was added to HARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 FOXI1 Eleanor Williams Source Expert Review Green was added to FOXI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 FDXR Eleanor Williams Source Expert Review Green was added to FDXR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 EPS8L2 Eleanor Williams Source Expert Review Green was added to EPS8L2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 DMXL2 Eleanor Williams Source Expert Review Green was added to DMXL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 COL9A2 Eleanor Williams Source Expert Review Green was added to COL9A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 COL9A1 Eleanor Williams Source Expert Review Green was added to COL9A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 COL4A6 Eleanor Williams Source Expert Review Amber was added to COL4A6.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Monogenic hearing loss v2.220 COL2A1 Eleanor Williams Source Expert Review Green was added to COL2A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 COL11A1 Eleanor Williams Source Expert Review Green was added to COL11A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 COCH Eleanor Williams Source Expert list was added to COCH.
Mode of inheritance for gene COCH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.220 CISD2 Eleanor Williams Source Expert Review Green was added to CISD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 CEP250 Eleanor Williams Source Expert Review Green was added to CEP250.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 CDC14A Eleanor Williams Source Expert Review Green was added to CDC14A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 ATP6V1B2 Eleanor Williams Source Expert Review Green was added to ATP6V1B2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.220 AIFM1 Eleanor Williams Source Expert Review Green was added to AIFM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v2.219 KCNE1 Arina Puzriakova Phenotypes for gene: KCNE1 were changed from Jervell and Lange-Nielsen syndrome 2, 612347; JLNS; Long QT syndrome-5, 613695 to Jervell and Lange-Nielsen syndrome 2, OMIM:612347
Monogenic hearing loss v2.218 ADGRV1 Ivone Leong Tag Q1_22_MOI tag was added to gene: ADGRV1.
Monogenic hearing loss v2.218 ADGRV1 Ivone Leong reviewed gene: ADGRV1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.218 GJB3 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: GJB3.
Monogenic hearing loss v2.218 SOX2 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: SOX2.
Monogenic hearing loss v2.218 SPATA5L1 Ivone Leong Phenotypes for gene: SPATA5L1 were changed from Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616 to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616; Deafness, autosomal recessive 119, OMIM:619615
Monogenic hearing loss v2.217 SPATA5L1 Ivone Leong Entity copied from Intellectual disability v3.1491
Monogenic hearing loss v2.217 SPATA5L1 Ivone Leong gene: SPATA5L1 was added
gene: SPATA5L1 was added to Hearing loss. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: SPATA5L1.
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Neurodevelopmental disorder with hearing loss and spasticity, OMIM:619616
Monogenic hearing loss v2.216 NLRP3 Arina Puzriakova Phenotypes for gene: NLRP3 were changed from Cold-induced autoinflammatory syndrome, familial, 120100; Coldinducedautoinflammatorysyndrome,familial,120100MuckleWellssyndrome,191900CINCAsyndrome,607115 to CINCA syndrome, OMIM:607115; Deafness, autosomal dominant 34, with or without inflammation, OMIM:617772; Muckle-Wells syndrome, OMIM:191900
Monogenic hearing loss v2.215 NLRP3 Arina Puzriakova Mode of inheritance for gene: NLRP3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.214 PBX1 Eleanor Williams Publications for gene: PBX1 were set to 28566479; 29036646
Monogenic hearing loss v2.213 PBX1 Eleanor Williams Mode of inheritance for gene: PBX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.212 PBX1 Eleanor Williams Tag Q4_21_rating tag was added to gene: PBX1.
Monogenic hearing loss v2.212 PBX1 Eleanor Williams changed review comment from: Comment on list classification: Promoting from grey to amber. 3 cases but in 1 case 7 other genes also deleted, and in another hearing loss was unilateral only.; to: Comment on list classification: Promoting from grey to amber. Deletions affecting more than just the PBX1 gene is reported for many, but in 3 cases only the PBX1 gene is affected. Recommend green rating following GMS review.
Monogenic hearing loss v2.212 PBX1 Eleanor Williams changed review comment from: Associated with Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay #617641 (AD) in OMIM.

3 cases with reported hearing loss among other anomalies, but in one case a further 7 genes are deleted, and in one case the hearing loss was unilateral only.

PMID: 28566479 - Heidet et al 2017 - performed targeted exome screening of candidate 330 genes in a cohort of 204 patients with CAKUT and 11 patients suspected to suffer from branchio-oto-renal syndrome. 2 out of 5 patients with heterozygous loss of function mutations/deletions in PBX1 are reported to have deafness in addition to a renal phenotype. In patient K175 there was a de novo heterozygous 1 bp deletion leading to a frameshift. In patient K1819 there was a de novo 2.46-Mb deletion removing the whole PBX1 gene along with 7 other genes. Further details about the loss of hearing phenotype are not given.

PMID: 29036646 - Slavotinek et al 2017 - report 8 patients with de novo, deleterious sequence variants in the PBX1. 3 had external ear abnormalities but only 1 is reported to have hearing loss and this is unilateral, mild to moderate conductive hearing loss. This patient was found to have a heterozygous, de novo indel c.783dupC, predicting (p.Ser262Glnfs*2 in PBX1.; to: Associated with Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay #617641 (AD) in OMIM.

3 cases reported where only the PBX1 gene is affected (indels or deletion covering only the PBX1 gene). In one of these cases the phenotype is syndromic but hearing loss is unilateral only. In 5 further cases hearing loss is reported and involve microdeletions covering more genes that just PBX1.

PMID: 28566479 - Heidet et al 2017 - performed targeted exome screening of candidate 330 genes in a cohort of 204 patients with CAKUT and 11 patients suspected to suffer from branchio-oto-renal syndrome. 2 out of 5 patients with heterozygous loss of function mutations/deletions in PBX1 are reported to have deafness in addition to a renal phenotype. In patient K175 there was a de novo heterozygous 1 bp deletion leading to a frameshift. In patient K1819 there was a de novo 2.46-Mb deletion removing the whole PBX1 gene along with 7 other genes. Further details about the loss of hearing phenotype are not given.

PMID: 29036646 - Slavotinek et al 2017 - report 8 patients with de novo, deleterious sequence variants in the PBX1. 3 had external ear abnormalities but only 1 is reported to have hearing loss and this is unilateral, mild to moderate conductive hearing loss. This patient was found to have a heterozygous, de novo indel c.783dupC, predicting (p.Ser262Glnfs*2 in PBX1.

PMID: 28270404 - Le Tanno et al 2017 - eight patients presenting with CAKUT carrying an 1q23.3q24.1 microdeletion. They defined a 276-kb minimal common region that only overlaps with the PBX1 gene. 5 patients presented with varying degrees of hearing impairment (no detailed assessments). Patient 8, in which the deletion only covers the PBX1 gene showed an obvious bilateral dysplasia leading to a conductive hearing defect.
Monogenic hearing loss v2.212 PBX1 Eleanor Williams Classified gene: PBX1 as Amber List (moderate evidence)
Monogenic hearing loss v2.212 PBX1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. 3 cases but in 1 case 7 other genes also deleted, and in another hearing loss was unilateral only.
Monogenic hearing loss v2.212 PBX1 Eleanor Williams Gene: pbx1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.211 PBX1 Eleanor Williams Phenotypes for gene: PBX1 were changed from Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM:617641; congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, MONDO:0060549
Monogenic hearing loss v2.210 PBX1 Eleanor Williams Publications for gene: PBX1 were set to
Monogenic hearing loss v2.209 PBX1 Eleanor Williams reviewed gene: PBX1: Rating: ; Mode of pathogenicity: None; Publications: 28566479, 29036646; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM:617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.209 PBX1 Dmitrijs Rots gene: PBX1 was added
gene: PBX1 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: PBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PBX1 were set to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay
Review for gene: PBX1 was set to GREEN
Added comment: Well known disease gene. As OMIM disease name suggests, hearing loss with ear abnormalities is common (reported in at least 5 cases).
Sources: Literature
Monogenic hearing loss v2.209 EDNRB Ivone Leong Added comment: Comment on mode of inheritance: MOI changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal" as patients with biallelic variants have a more severe phenotype. This MOI change does not affect tiering.
Monogenic hearing loss v2.209 EDNRB Ivone Leong Mode of inheritance for gene: EDNRB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Monogenic hearing loss v2.208 EDN3 Ivone Leong Added comment: Comment on mode of inheritance: MOI changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal" as patients with biallelic variants have a more severe phenotype. This MOI change does not affect tiering.
Monogenic hearing loss v2.208 EDN3 Ivone Leong Mode of inheritance for gene: EDN3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Monogenic hearing loss v2.207 PRRX1 Arina Puzriakova Phenotypes for gene: PRRX1 were changed from to Agnathia-otocephaly complex, OMIM:202650
Monogenic hearing loss v2.206 COL9A3 Arina Puzriakova Phenotypes for gene: COL9A3 were changed from Stickler syndrome to Stickler syndrome, MONDO:0019354
Monogenic hearing loss v2.205 COL9A2 Arina Puzriakova Phenotypes for gene: COL9A2 were changed from ?Stickler syndrome, type V, 614284 to Stickler syndrome, type V, OMIM:614284
Monogenic hearing loss v2.204 COL9A1 Arina Puzriakova Phenotypes for gene: COL9A1 were changed from Stickler syndrome, type IV, 614134; hearing loss to Stickler syndrome, type IV, OMIM:614134; Hearing loss
Monogenic hearing loss v2.203 COL9A1 Arina Puzriakova Mode of inheritance for gene: COL9A1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.202 COL4A4 Arina Puzriakova Phenotypes for gene: COL4A4 were changed from Alport syndrome, autosomal recessive, 203780Hematuria,familial benign; Alportsyndrome,autosomalrecessive,203780Hematuria,familialbenign to Alport syndrome 2, autosomal recessive, OMIM:203780; Hematuria,familial benign, OMIM:141200
Monogenic hearing loss v2.201 COL11A1 Arina Puzriakova Phenotypes for gene: COL11A1 were changed from Stickler syndrome, type II, MIM#604841; Deafness, autosomal dominant 37, MIM#618533 to Deafness, autosomal dominant 37, OMIM:618533; Stickler syndrome, type II, OMIM:604841
Monogenic hearing loss v2.200 GGPS1 Ivone Leong Entity copied from Congenital muscular dystrophy v2.18
Monogenic hearing loss v2.200 GGPS1 Ivone Leong gene: GGPS1 was added
gene: GGPS1 was added to Hearing loss. Sources: Literature,Expert Review Amber
Q4_21_rating tags were added to gene: GGPS1.
Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GGPS1 were set to 32403198
Phenotypes for gene: GGPS1 were set to Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome, OMIM:619518
Monogenic hearing loss v2.199 SARS Ivone Leong Tag watchlist was removed from gene: SARS.
Tag new-gene-name tag was added to gene: SARS.
Monogenic hearing loss v2.199 SARS Ivone Leong Tag new-gene-name was removed from gene: SARS.
Monogenic hearing loss v2.199 SARS Ivone Leong Classified gene: SARS as Red List (low evidence)
Monogenic hearing loss v2.199 SARS Ivone Leong Added comment: Comment on list classification: Demoted from Amber to Red as only 1 of the cases had hearing loss.
Monogenic hearing loss v2.199 SARS Ivone Leong Gene: sars has been classified as Red List (Low Evidence).
Monogenic hearing loss v2.198 SARS Ivone Leong Entity copied from Intellectual disability v3.1356
Monogenic hearing loss v2.198 SARS Ivone Leong gene: SARS was added
gene: SARS was added to Hearing loss. Sources: Expert Review Amber,Literature
watchlist, new-gene-name tags were added to gene: SARS.
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 28236339; 34570399
Phenotypes for gene: SARS were set to ?Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709
Monogenic hearing loss v2.197 SLC29A3 Arina Puzriakova Phenotypes for gene: SLC29A3 were changed from Histiocytosis-lymphadenopathy plus syndrome; Hyperpigmentation, Cutaneous, with Hypertrichosis, Hepatosplenomegaly, Heart Anomalies, Hearing Loss, and Hypogonadism to Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782; Hyperpigmentation, Cutaneous, with Hypertrichosis, Hepatosplenomegaly, Heart Anomalies, Hearing Loss, and Hypogonadism
Monogenic hearing loss v2.196 CEACAM16 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving mode of inheritance as monoallelic for now but with recommendation for changing to both mono and biallelic after GMS review. 3 reported cases with homozygous variants.
Monogenic hearing loss v2.196 CEACAM16 Eleanor Williams Mode of inheritance for gene: CEACAM16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.195 CEACAM16 Eleanor Williams Tag Q4_21_MOI tag was added to gene: CEACAM16.
Monogenic hearing loss v2.195 CEACAM16 Eleanor Williams edited their review of gene: CEACAM16: Added comment: Further heterozygous cases:
PMID: 33040498 - Zhang et al 2020 - a heterozygous missense mutation, c.418A>G/p. Thr140Ala in the CEACAM16 gene, segregating with the deafness in this Chinese family. Abstract only accessed.

Homozygous cases:
PMID: 29703829 - Booth et al 2018 - 2 Iranian families with progressive mild-to-moderate hearing loss reported, in which homozygous splice variants ( c.662-1G>C and c.37G>T) were found in CEACAM16. In both families the variant segregated with the phenotype. Heterozygous carriers had normal hearing. Both variants are absent from gnomAD and ExAC.

PMID: 30514912 - Dias et al 2019 - novel and extremely rare loss-of-function variant c.436 C > T/p.(Arg146Ter) in the CEACAM16 gene segregating with post-lingual progressive autosomal recessive hearing loss in 3 individuals from a Brazilian family. This variant is predicted to significantly reduce the size of the wild type protein.; Changed publications to: 33040498, 29703829, 30514912; Changed phenotypes to: Deafness, autosomal recessive 113, OMIM:618410, deafness, autosomal recessive 113, MONDO:0032732, Deafness, autosomal dominant 4B, OMIM:614614, autosomal dominant nonsyndromic deafness 4B, MONDO:0013823; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.195 CLDN9 Eleanor Williams Classified gene: CLDN9 as Amber List (moderate evidence)
Monogenic hearing loss v2.195 CLDN9 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber but with a green rating recommendation following GMS review. 3 unrelated cases plus mouse model and some functional data.
Monogenic hearing loss v2.195 CLDN9 Eleanor Williams Gene: cldn9 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.194 CLDN9 Eleanor Williams Phenotypes for gene: CLDN9 were changed from to Deafness, autosomal recessive 116, OMIM:619093; deafness, autosomal recessive 116, MONDO:0033670
Monogenic hearing loss v2.193 CLDN9 Eleanor Williams Publications for gene: CLDN9 were set to
Monogenic hearing loss v2.192 CLDN9 Eleanor Williams Mode of inheritance for gene: CLDN9 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.191 CLDN9 Eleanor Williams Tag Q4_21_rating tag was added to gene: CLDN9.
Monogenic hearing loss v2.191 CLDN9 Eleanor Williams reviewed gene: CLDN9: Rating: GREEN; Mode of pathogenicity: None; Publications: 31175426, 34265170; Phenotypes: Deafness, autosomal recessive 116, OMIM:619093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.191 USP48 Eleanor Williams Tag watchlist was removed from gene: USP48.
Tag Q4_21_rating tag was added to gene: USP48.
Monogenic hearing loss v2.191 USP48 Eleanor Williams Classified gene: USP48 as Amber List (moderate evidence)
Monogenic hearing loss v2.191 USP48 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber, with a recommendation for green rating following GMS review. 3 cases, 1 with segregation data (incomplete penetrance), plus supportive zebrafish model.
Monogenic hearing loss v2.191 USP48 Eleanor Williams Gene: usp48 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.190 USP48 Eleanor Williams Phenotypes for gene: USP48 were changed from non-syndromic hearing loss to non-syndromic hearing loss; nonsyndromic genetic deafness, MONDO:0019497
Monogenic hearing loss v2.189 USP48 Eleanor Williams Publications for gene: USP48 were set to
Monogenic hearing loss v2.188 USP48 Eleanor Williams Mode of inheritance for gene: USP48 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.187 USP48 Eleanor Williams edited their review of gene: USP48: Added comment: PMID: 34059922 - Bassani et al 2021 - 3 cases reported with variants in USP48 and non syndromic hearing loss. They first analysed 4-generation Italian family with 6 individuals with hearing loss. The only rare variant segregating with the disease was a missense variant in USP48 (NM_032234.7:c.1216G > A, NP_115612.4:p.(Gly406Arg)). The variant is present in GnomAD v2.1.1 with a minor allele frequency (MAF) of 6.7 × 10−5 (17 allele out of 251 304 with no homozygotes). They also observed one hearing individual in the family who was heterozygous for the variant, suggesting incomplete penetrance.
In a Dutch family the found by exome sequencing a missense variant in USP48 (NM_032236.7:c.2215_2216delinsTT, NP_115612.4:p.(Thr739Leu)). The probands mother and uncle were also affected by no sequence data was available for analysis.
In a French family a proband is reported with right profound sensorineural hearing impairment (at 12 months), but normal left hearing (at 6 years old). The patient is heterozygote for a de novo splice variant in USP48 (NM_032236.7:c.3058 + 2 T > C, NP_115612.4:p.?;) which is not found in GnomAD and is predicted to result in a frameshift resulting in either NMD or a truncated protein.
In functional experiments they showed that the two missense variants found in the Italian and Dutch families, and a shortened protein as predicted for the variant found in the French variant, showed an impaired ability to cleave tetra-ubiquitin into tri-, di- and mono-ubiquitin. Using immunohistology, they show that the human USP48 protein is present in fetal inner ear specimens.
In addition zebrafish lacking usp48 showed a significant decrease of auditory response in acoustic startle response assays at 600 and 800 Hz wavelengths.; Changed rating: GREEN; Changed publications to: 34059922; Changed phenotypes to: nonsyndromic genetic deafness, MONDO:0019497; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.187 RNF220 Ivone Leong Phenotypes for gene: RNF220 were changed from Intellectual disability, MONDO:0001071 to Sensorineural hearing impairment, HP:0000407
Monogenic hearing loss v2.186 RNF220 Ivone Leong Tag Q4_21_rating tag was added to gene: RNF220.
Monogenic hearing loss v2.186 RNF220 Ivone Leong changed review comment from: Comment on list classification: New gene added by Konstantinos Varvagiannis. This gene is currently not associated with a phenotype in OMIM or Gene2Phenotype. There are >3 cases for this gene; however, 3 of the cases described in PMID:33964137 are of Roma descent and haplotype analysis has shown that the variant found in these families are due to a founder effect (c.1094G>A, p.Arg365Gly). A separate Roma family also has the same variant (c.1094G>A, p.Arg365Gly). An Italian family with similar phenotypes has a different variant (c.1088G>A, p.Arg363Gly). The authors also report on in vitro and in vivo studies.

There is enough evidence to support a gene-disease association; however, the ID severity in these patients do not meet the criteria (moderate to severe) for this panel (patients show mild (mostly) to moderate severity). Therefore, this gene has been given an Amber rating.; to: Comment on list classification: New gene added by Konstantinos Varvagiannis. This gene is currently not associated with a phenotype in OMIM or Gene2Phenotype. There are >3 cases for this gene; however, 3 of the cases described in PMID:33964137 are of Roma descent and haplotype analysis has shown that the variant found in these families are due to a founder effect (c.1094G>A, p.Arg365Gly). A separate Roma family also has the same variant (c.1094G>A, p.Arg365Gly). An Italian family with similar phenotypes has a different variant (c.1088G>A, p.Arg363Gly). The authors also report on in vitro and in vivo studies.

There is enough evidence to support a gene-disease association. Therefore, this gene should be Green at the next review.
Monogenic hearing loss v2.186 RNF220 Ivone Leong Entity copied from Intellectual disability v3.1329
Monogenic hearing loss v2.186 RNF220 Ivone Leong gene: RNF220 was added
gene: RNF220 was added to Hearing loss. Sources: Literature,Expert Review Amber,Other
Mode of inheritance for gene: RNF220 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF220 were set to 33964137; 10881263
Phenotypes for gene: RNF220 were set to Intellectual disability, MONDO:0001071
Penetrance for gene: RNF220 were set to Complete
Monogenic hearing loss v2.185 HARS2 Ivone Leong Phenotypes for gene: HARS2 were changed from #614926:?Perrault syndrome 2 to Perrault syndrome 2, OMIM:614926
Monogenic hearing loss v2.184 HARS2 Ivone Leong Publications for gene: HARS2 were set to 12056811; 15779907; 21464306; 517579; 7755634; 27650058
Monogenic hearing loss v2.183 JAG1 Arina Puzriakova Mode of inheritance for gene: JAG1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v2.182 JAG1 Arina Puzriakova Phenotypes for gene: JAG1 were changed from Alagille syndrome, 118450Deafness, congenital heart defects and posterior embryotoxonTetralogy of Fallot, 187500; Alagillesyndrome,118450TetralogyofFallot,187500Deafness,congenitalheartdefects,andposteriorembryotoxon to ?Deafness, congenital heart defects, and posterior embryotoxon, OMIM:617992
Monogenic hearing loss v2.181 GJA1 Arina Puzriakova Phenotypes for gene: GJA1 were changed from to Craniometaphyseal dysplasia, autosomal recessive, OMIM:218400
Monogenic hearing loss v2.180 HARS2 Bill Newman reviewed gene: HARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID:34406847, 34338890); Phenotypes: sensorineural hearing loss, primary ovarian insufficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.180 SERAC1 Arina Puzriakova Phenotypes for gene: SERAC1 were changed from 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739
Monogenic hearing loss v2.179 CLDN9 Zornitza Stark reviewed gene: CLDN9: Rating: GREEN; Mode of pathogenicity: None; Publications: 31175426, 19696885, 34265170; Phenotypes: Deafness, autosomal recessive 116, MIM#619093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.179 ATP6V0A4 Arina Puzriakova Publications for gene: ATP6V0A4 were set to
Monogenic hearing loss v2.178 ATP6V0A4 Arina Puzriakova Phenotypes for gene: ATP6V0A4 were changed from to Distal renal tubular acidosis 3, with or without sensorineural hearing loss, OMIM:602722
Monogenic hearing loss v2.177 P2RX2 Eleanor Williams reviewed gene: P2RX2: Rating: ; Mode of pathogenicity: None; Publications: 33791800; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v2.177 KDM3B Ivone Leong changed review comment from: After consulting with the Genomics England Clinical Team it was decided that this gene should be promoted to Green status at the next review.; to: After consulting with the Genomics England Clinical Team it was decided that this gene should be added to this panel. However, there is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Monogenic hearing loss v2.177 KDM3B Ivone Leong Tag Q2_21_rating was removed from gene: KDM3B.
Tag watchlist tag was added to gene: KDM3B.
Monogenic hearing loss v2.177 KDM3B Ivone Leong Entity copied from Intellectual disability v3.1146
Monogenic hearing loss v2.177 KDM3B Ivone Leong gene: KDM3B was added
gene: KDM3B was added to Hearing loss. Sources: Victorian Clinical Genetics Services,Expert Review Amber
Q2_21_rating tags were added to gene: KDM3B.
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KDM3B were set to 30929739
Phenotypes for gene: KDM3B were set to Global developmental delay; Intellectual disability; Short stature; Behavioral abnormality; Seizures
Monogenic hearing loss v2.176 ADGRV1 Ivone Leong Publications for gene: ADGRV1 were set to PMID:10234513; 10976914; 11545713; 11606593; 12095917; 12402266; 14740321; 15820310; 18854872; 19357116; 19357117; 20440071; 22147658; 9598305; 9734811
Monogenic hearing loss v2.175 ZPR1 Ivone Leong Entity copied from Growth failure in early childhood v1.70
Monogenic hearing loss v2.175 ZPR1 Ivone Leong gene: ZPR1 was added
gene: ZPR1 was added to Hearing loss. Sources: Literature,Expert Review Red
founder-effect tags were added to gene: ZPR1.
Mode of inheritance for gene: ZPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPR1 were set to 29851065
Phenotypes for gene: ZPR1 were set to ?Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies, OMIM:619321
Monogenic hearing loss v2.174 COL9A3 Ivone Leong reviewed gene: COL9A3: Rating: ; Mode of pathogenicity: None; Publications: 33633367; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v2.174 GREB1L Eleanor Williams Classified gene: GREB1L as Amber List (moderate evidence)
Monogenic hearing loss v2.174 GREB1L Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating following GMS review. 4 cases with non-syndromic hearing loss now reported.
Monogenic hearing loss v2.174 GREB1L Eleanor Williams Gene: greb1l has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.173 GREB1L Eleanor Williams Tag Q2_21_rating tag was added to gene: GREB1L.
Monogenic hearing loss v2.173 GREB1L Eleanor Williams Phenotypes for gene: GREB1L were changed from Deafness, autosomal dominant 80, MIM# 619274 to Deafness, autosomal dominant 80 OMIM:619274; deafness, autosomal dominant 80, MONDO:0030998
Monogenic hearing loss v2.172 GREB1L Eleanor Williams Publications for gene: GREB1L were set to 29955957; 32585897
Monogenic hearing loss v2.171 GREB1L Eleanor Williams edited their review of gene: GREB1L: Changed rating: GREEN; Changed publications to: 29955957, 32585897, 29100090; Changed phenotypes to: Deafness, autosomal dominant 80 OMIM:619274, deafness, autosomal dominant 80, MONDO:0030998; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.171 GREB1L Eleanor Williams commented on gene: GREB1L
Monogenic hearing loss v2.171 CRYM Eleanor Williams Classified gene: CRYM as Red List (low evidence)
Monogenic hearing loss v2.171 CRYM Eleanor Williams Added comment: Comment on list classification: Leaving rating as red but with green recommendation following GMS review. 3 cases now reported, 1 in a family of significant size. Expression data to show that this protein is express in the ear.
Monogenic hearing loss v2.171 CRYM Eleanor Williams Gene: crym has been classified as Red List (Low Evidence).
Monogenic hearing loss v2.170 CRYM Eleanor Williams Tag Q2_21_rating tag was added to gene: CRYM.
Monogenic hearing loss v2.170 CRYM Eleanor Williams Phenotypes for gene: CRYM were changed from hearing loss; Deafness, autosomal dominant 40 to Deafness, autosomal dominant 40, OMIM:616357; autosomal dominant nonsyndromic deafness 40, MONDO:0014603
Monogenic hearing loss v2.169 CRYM Eleanor Williams Publications for gene: CRYM were set to 12471561; 1384048; 1478656; 16740909; 9328354
Monogenic hearing loss v2.168 CRYM Eleanor Williams edited their review of gene: CRYM: Added comment: Associated with Deafness, autosomal dominant 40 #616357 (AD) in OMIM.

PMID: 32742378 - Wang et al 2020 - report a 4 generation Chinese family with 31 members, of which 7 have hearing loss. WES identified a heterozygous missense mutation in CRYM (c.152C>T; Pro51Leu) which segregated with the phenotype in the family. As Zornitza Stark reports gnomad (3.1.1) has 2 hets reported (allele freq of 1.32e-5).

PMID: 12471561 - Abe et al 2003 - used genome-wide cDNA microarray analysis to investigate gene-expression profiles in human cochlea and vestibule and identified CRYM as a candidate gene. They then screened CRYM, among 192 patients with nonsyndromic deafness. Two unrelated Japanese patients were identified with variants in CRYM; one with a de novo change (c.945A→T, p.X315Y) which results in an extended protein in a patient with unaffected parents, and the other was a missense mutation (c.941A→C;p.K314T) that segregated dominantly in the proband’s family.

PMID: 16740909 - Oshima et al 2006 - looked at the effect of the two variants found by Abe et al, X315Y and K314T by looking at T3 binding activity of the mutant μ‐crystallin (product of CRYM) proteins. They found the K314T mutation impaired the NADPH dependent T3 binding (but did not find this for the X315Y variant). They also showed that μ‐crystallin protein localisation in mouse cochlea using immunocytochemical methods.

PMID: 18448257 - Usami et al 2009 - showed that Crym protein localizes in type II fibrocytes of the spiral ligament in the cochlea in mice and rats

PMID: 24676347 - Yoshimura et al 2014 - show a gradient of gene expression of CRYM in mouse cochlea

PMID: 26915689 - Hosoya et al 2016 - immunohistochemical analysis of expression of CRYM in cochlea of a non-human primate, the common marmoset and found a different expression pattern compared to mouse, with expression not only in the lateral wall spiral ligament and the spiral limbus, but also in both inner and outer hair cells, supporting cells.; Changed publications to: 32742378, 12471561, 16740909, 18448257, 24676347, 26915689; Changed phenotypes to: Deafness, autosomal dominant 40, OMIM:616357, autosomal dominant nonsyndromic deafness 40, MONDO:0014603; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.168 CLRN2 Eleanor Williams Classified gene: CLRN2 as Amber List (moderate evidence)
Monogenic hearing loss v2.168 CLRN2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber as there is one extended family reported with variants in this gene, plus some supporting functional data.
Monogenic hearing loss v2.168 CLRN2 Eleanor Williams Gene: clrn2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.167 CLRN2 Eleanor Williams Phenotypes for gene: CLRN2 were changed from Non-syndromic hearing loss to ?Deafness, autosomal recessive 117, OMIM:619174; deafness, autosomal recessive 117, MONDO:0030905
Monogenic hearing loss v2.166 CLRN2 Eleanor Williams reviewed gene: CLRN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33496845; Phenotypes: Deafness, autosomal recessive 117, OMIM:619174, deafness, autosomal recessive 117, MONDO:0030905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.166 STXBP3 Arina Puzriakova Entity copied from Primary immunodeficiency v2.425
Monogenic hearing loss v2.166 STXBP3 Arina Puzriakova gene: STXBP3 was added
gene: STXBP3 was added to Hearing loss. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: STXBP3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STXBP3 were set to 33346580; https://doi.org/10.1053/j.gastro.2017.11.120; 33891011
Phenotypes for gene: STXBP3 were set to Very Early Onset Inflammatory Bowel Disease; Sensorineural hearing loss
Penetrance for gene: STXBP3 were set to unknown
Monogenic hearing loss v2.165 APOPT1 Arina Puzriakova Publications for gene: APOPT1 were set to
Monogenic hearing loss v2.164 APOPT1 Arina Puzriakova Mode of inheritance for gene: APOPT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.163 APOPT1 Arina Puzriakova Phenotypes for gene: APOPT1 were changed from Mitochondrial Complex IV Deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 17, OMIM:619061
Monogenic hearing loss v2.162 GREB1L Zornitza Stark gene: GREB1L was added
gene: GREB1L was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREB1L were set to 29955957; 32585897
Phenotypes for gene: GREB1L were set to Deafness, autosomal dominant 80, MIM# 619274
Review for gene: GREB1L was set to GREEN
gene: GREB1L was marked as current diagnostic
Added comment: DFNA80 is characterized by nonsyndromic congenital deafness associated with absent or malformed cochleae and eighth cranial nerves.

Four unrelated families reported, no comment on a renal phenotype. Note variants in this gene are also associated with renal agenesis.
Sources: Literature
Monogenic hearing loss v2.162 AP1S1 Ivone Leong Classified gene: AP1S1 as Amber List (moderate evidence)
Monogenic hearing loss v2.162 AP1S1 Ivone Leong Gene: ap1s1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.161 AP1S1 Ivone Leong gene: AP1S1 was added
gene: AP1S1 was added to Hearing loss. Sources: Literature
Q2_21_rating tags were added to gene: AP1S1.
Mode of inheritance for gene: AP1S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1S1 were set to 32306098; 15668823; 19057675; 23423674; 30244301
Phenotypes for gene: AP1S1 were set to Non-syndromic congenital intestinal failure; MEDNIK syndrome, OMIM:609313
Review for gene: AP1S1 was set to GREEN
Added comment: This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. This gene is also Amber with a recommendation to promote to Green on the Intestinal failure panel (Version 1.40) with the following reviews:

" Established gene-disease association with MEDNIK syndrome - PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease - 2 consanguineous families, each carrying a homozygous missense AP1S1 variant - AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense variants. Sources: Literature
Zornitza Stark (Australian Genomics), 5 Oct 2020"

"This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. After discussion with the Genomics England Clinical Team it was decided that it was appropriate to consider all evidence (including the cases that have an intestinal phenotype for this gene - MEDNIK syndrome), therefore, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review."

After discussion with the Genomics England Clinical Team it was decided that this gene should also be included in this panel.
Sources: Literature
Monogenic hearing loss v2.160 LOXHD1 Arina Puzriakova Publications for gene: LOXHD1 were set to PMID:16936105; 19732867; 21465660; 22341973
Monogenic hearing loss v2.159 LOXHD1 Arina Puzriakova Phenotypes for gene: LOXHD1 were changed from Nonsyndromic Hearing Loss, Recessive; Deafness, autosomal recessive 77, 613079; hearing loss to Deafness, autosomal recessive 77, OMIM:613079
Monogenic hearing loss v2.158 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from #615300: Perrault syndrome 4 to Perrault syndrome 4, OMIM:615300
Monogenic hearing loss v2.157 POLD1 Arina Puzriakova Phenotypes for gene: POLD1 were changed from {Colorectal cancer, susceptibility to, 10}, 612591Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome,615381; Colorectalcancer,susceptibilityto,10},612591Mandibularhypoplasia,deafness,progeroidfeatures,andlipodystrophysyndrome,615381 to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, OMIM:615381
Monogenic hearing loss v2.156 CRYM Zornitza Stark reviewed gene: CRYM: Rating: GREEN; Mode of pathogenicity: None; Publications: 32742378, 12471561, 16740909, 18448257, 24676347, 26915689; Phenotypes: Deafness, autosomal dominant 40 MIM#616357; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v2.156 MYO15A Eleanor Williams Phenotypes for gene: MYO15A were changed from Nonsyndromic Hearing Loss, Recessive; Deafness, autosomal recessive 3, 600316; hearing loss to Deafness, autosomal recessive 3 OMIM:600316; autosomal recessive nonsyndromic deafness 3 MONDO:0010860
Monogenic hearing loss v2.155 MYO15A Eleanor Williams Publications for gene: MYO15A were set to PMID:10552926; 10915760; 11735029; 12966030; 15590698; 15654330; 17546645; 17851452; 17853461; 21236676; 7704031; 9603735; 9603736
Monogenic hearing loss v2.154 MYO15A Eleanor Williams reviewed gene: MYO15A: Rating: ; Mode of pathogenicity: None; Publications: 33078831; Phenotypes: Deafness, autosomal recessive 3 OMIM:600316, autosomal recessive nonsyndromic deafness 3 MONDO:0010860; Mode of inheritance: None
Monogenic hearing loss v2.154 MYO3A Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as biallelic, but note that 2 independent cases of monallelic inheritance have been reported.
Monogenic hearing loss v2.154 MYO3A Eleanor Williams Mode of inheritance for gene: MYO3A was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.153 MYO3A Eleanor Williams Phenotypes for gene: MYO3A were changed from Nonsyndromic Hearing Loss, Recessive; Deafness, autosomal recessive 30, 607101; hearing loss to Deafness, autosomal recessive 30 OMIM:607101; autosomal recessive nonsyndromic deafness 30 MONDO:0011774
Monogenic hearing loss v2.152 MYO3A Eleanor Williams Publications for gene: MYO3A were set to PMID:10936054; 12032315; 21165622
Monogenic hearing loss v2.151 MYO3A Eleanor Williams reviewed gene: MYO3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33078831, 26841241, 29880844; Phenotypes: Deafness, autosomal recessive 30 OMIM:607101, autosomal recessive nonsyndromic deafness 30 MONDO:0011774; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.151 COL9A3 Eleanor Williams Classified gene: COL9A3 as Amber List (moderate evidence)
Monogenic hearing loss v2.151 COL9A3 Eleanor Williams Added comment: Comment on list classification: Leaving the rating as amber, but there are now 4 cases with homozygous variants in this gene in patients with hearing loss. 2 cases are reported with Stickler syndrome. In the other 2 cases Stickler syndrome was not excluded. The phenotype needs to be reviewed to decide whether to encompass Stickler syndrome genes on this panel.
Monogenic hearing loss v2.151 COL9A3 Eleanor Williams Gene: col9a3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.150 COL9A3 Eleanor Williams Added comment: Comment on mode of inheritance: Leaving as Biallelic mode of inheritance as 4 cases reported with this inheritance pattern. However PMID: 15917166 also reports two cases with an AD pattern of inheritance, but no segregation data to support this.
Monogenic hearing loss v2.150 COL9A3 Eleanor Williams Mode of inheritance for gene: COL9A3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.149 COL9A3 Eleanor Williams Tag Q2_21_phenotype tag was added to gene: COL9A3.
Monogenic hearing loss v2.149 COL9A3 Eleanor Williams edited their review of gene: COL9A3: Changed rating: GREEN
Monogenic hearing loss v2.149 COL9A3 Eleanor Williams edited their review of gene: COL9A3: Added comment: PMID: 33078831 - Wonkam et al 2020 - report 2 unrelated patients from Cameroon with autosomal recessive non-syndromic hearing impairment and a homozygous c.G406A, p.G136S variant in COL9A3. This variant is rare (ExAC_AFR MAF = 0, ExAC_ASI MAF = 0.001, Cameroonian controls MAF (N = 129) = 0). However, the authors report that further investigation of these patients is needed to exclude Stickler syndrome.

PMID: 15917166 - Asamura et al 2005 - direct-sequencing of COL9A3 gene in 159 non-syndromic sensorineural deafness patients (Japanese and Korean) and 150 normal controls. 2 possible disease-causing mutations were identified in patients with moderate progressive bilateral sensorineural hearing impairment in all frequencies. : a homozygous in-frame deletion of three amino acid residues (G181-P183 del) in one patient (with consanguineous parents) and a heterozygous missense mutation (D617E) found in 2 independent autosomal dominant families. No segregation data.; Changed publications: 31090205, 24273071, 33078831, 15917166; Changed phenotypes: Stickler syndrome, non-syndromic sensorineural deafness
Monogenic hearing loss v2.149 NCOA3 Eleanor Williams gene: NCOA3 was added
gene: NCOA3 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: NCOA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NCOA3 were set to 33326993
Phenotypes for gene: NCOA3 were set to non-syndromic hearing loss
Review for gene: NCOA3 was set to RED
Added comment: PMID: 33326993 - Salazar da Silva et al 2020 - report a 5 generation Brazilian family with 15 individuals with non-syndromic, bilateral and progressive hearing loss. Using linkage analysis and then exome sequencing they identified a heterozygous variant in NCOA3 (NM_181659, c.2810C > G; p.Ser937Cys) that was found in the 7 analysed affected individuals. It was also found in 4 unaffected individuals but they are within the range of onset of hearing loss observed in the family. Expression of nco3 was found in the inner ear of mice and zebrafish. ncoa3-/- zebrafish showed subtle alterations in cartilage, mineral density and abnormal adult swimming behaviour, which may suggest the mechanism of pathogenicity.
Sources: Literature
Monogenic hearing loss v2.148 PDSS1 Ivone Leong Classified gene: PDSS1 as Amber List (moderate evidence)
Monogenic hearing loss v2.148 PDSS1 Ivone Leong Gene: pdss1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.147 PDSS1 Ivone Leong gene: PDSS1 was added
gene: PDSS1 was added to Hearing loss. Sources: Literature
watchlist tags were added to gene: PDSS1.
Mode of inheritance for gene: PDSS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDSS1 were set to 33285023; 17332895
Phenotypes for gene: PDSS1 were set to Coenzyme Q10 deficiency, primary, 2, OMIM:614651
Review for gene: PDSS1 was set to AMBER
Added comment: Reviews copied from Optic neuropathy panel (Version 2.35).

"Two families reported where optic atrophy and deafness are part of the phenotype. Sources: Literature
Zornitza Stark (Australian Genomics), 1 Feb 2021"

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. As there are only 2 cases there is not enough evidence to support a gene-disease association. Therefore, this gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 9 Feb 2021"
Sources: Literature
Monogenic hearing loss v2.146 CLRN2 Zornitza Stark gene: CLRN2 was added
gene: CLRN2 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: CLRN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLRN2 were set to 33496845
Phenotypes for gene: CLRN2 were set to Non-syndromic hearing loss
Review for gene: CLRN2 was set to AMBER
Added comment: Missense variant segregates with non-syndromic hearing loss in 3 members of a consanguineous family, two from one nuclear family and one from another. The variant was also shown to result in some transcripts being abnormally spliced, resulting in a premature stop codon.

Functional studies in zebrafish and mice show the gene plays an essential role in normal organization and maintenance of the auditory hair bundles, and for hearing function.

Rated Amber due to supporting functional studies in mice.
Sources: Literature
Monogenic hearing loss v2.146 COL9A3 Eleanor Williams commented on gene: COL9A3: Removed the for-review tag as this gene is not a candidate for promoting to green as there are only two cases. However, once a decision is made about including Stickler syndrome green genes (e.g. COL9A1) or not on this panel, this gene may need further revision as regards to rating.
Monogenic hearing loss v2.146 MN1 Arina Puzriakova Phenotypes for gene: MN1 were changed from CEBALID syndrome, 618774 to CEBALID syndrome, OMIM:618774; CEBALID syndrome, MONDO:0032908
Monogenic hearing loss v2.145 GJB3 Eleanor Williams Classified gene: GJB3 as Green List (high evidence)
Monogenic hearing loss v2.145 GJB3 Eleanor Williams Added comment: Comment on list classification: Leaving rating as green for now, but with recommendation of review at the next GMS update.
Monogenic hearing loss v2.145 GJB3 Eleanor Williams Gene: gjb3 has been classified as Green List (High Evidence).
Monogenic hearing loss v2.144 GJB3 Eleanor Williams Tag for-review tag was added to gene: GJB3.
Monogenic hearing loss v2.144 GJB3 Eleanor Williams changed review comment from: GJB3 - nonsyndromic genetic deafness association DISPUTED in ClinGen.

A large number of early studies have looked at GJB3 variants in HL patients. In all cases targeted screening of hearing loss genes was performed, with only a few genes looked at in most cases. At least 17 protein altering variants have been reported, but with no or limited segregation data. Two variants (NM_001005752.1:c.94C>T, Arg32Trp and c.598G>A, Val200Ile) are found at high allele frequency in the general population (both >0.02 gnomad v3.1) and c.529T>G, Tyr177Asp at a fairly high frequency (0.005535). 14 other variants are either not present in gnomad, or found at low frequency (< 0.0005). There is some data to support a functional change in proteins with 5 of the variants but no animal knockout model has been reported. One variant ((Ile141Val) found in a compound het case (Lui et al 2000) was found to migrate in cell

Monoallelic cases:
PMID:9843210 - Xia et al. 1998 - report monallelic variants found in GJB3 in 2 families with sensorineural deafness. Only the GJB3 gene was sequenced. In both families some carriers were unaffected. The two variants are ENST00000373362.3:c.547G>A GLU183LYS, ENST00000373362.3:c.538C>T (ARG180TER).

PMID:12630965 - Mhatre et al. 2003 - assessed 63 individuals with non-syndromic sporadic hearing impairment for CX31 (GJB3) mutations. 15 out of 63 patients (24%) had variants but only one variant was protein altering (C94T, R32W). This was found in two unrelated individuals with late onset hearing loss.

PMID: 10790215 - López-Bigas et al 2000 - report the molecular analysis of GJB3 in 153 patients with deafness and 110 with peripheral neuropathy. Identified two amino acid changes in patients; R32W and V200I. However, the R32W change was also detected in 18% of control subjects.

PMID:12791041 - Uyguner et al. 2003; Screened 60 Turkish patients with autosomal‐recessive NSSHL for variants in GJB2, GJB3, GJA1, DeltaGJB6-D13S1830 and CLDN14. A novel heterozygous variant, C667A;P223T, in GJB3 was found in a family with two affected children. However, the non-affected father also carried this variant. The authors suggest they may carry a second non-identified variant in a functionally related gene.

PMID:15131355 - Alexandrino et al. 2004 - analysed the GJB3 gene in 67 families with sporadic nonsyndromic hearing impairment. They found three amino acid changes: Y177D (c.529T > G), 49delK (c.144-146delGAA), and R32W (c.1227C > T). Abstract only accessed.

PMID:17259707 - Yang et al. 2007 - screened 260 Taiwanese individuals with nonsyndromic deafness and 120 with normal hearing. 8 genes were looked at GJB2, GJE1, GJB6, GJB4, GJB3, GJB1, GJA1 and pseudogene rho GJA1. A novel variant was identified GJB3 in 3 patients with nonsyndromic deafness. Abstract only accessed.

PMID:19744334 - Yuan et al. 2009 - screened 284 unrelated school children with hearing loss, and 200 control patients for variants in GJB2, GJB3, GJB6, SLC26A4, 12S rRNA, and tRNAser(UCN) genes. 2 patients were found with heterozygous protein altering variants that were not found in controls; c.24_49ins26bp (results in frameshift), c.497A>G, N166S. However, the patient carrying N166S mutation in one allele was verified to carry GJB2 235delC mutation in the other. Parental DNA was not available for the patient with the c.24_49ins26bp variant.

PMID:22617145 - Oh et al. 2013 - looked at GJB3 and GJB6 in 215 unrelated Korean nonsyndromic sensorineural HL patients. 7 variants were identified in GJB3. 2 variants (c.79G>A,p.V27M and c.250G>A,p.V84I) were not observed in normal Korean controls. Functional tests showed that these two variants did not functional normally when each was expressed as a heterozygote with the wild-type Cx31.

PMID: 23638949 - Yao et al 2013 - screened 227 segregating deaf students and 200 individuals with normal hearing for variants in GJB2, GJB3, SLC26A4, and mtDNA m.C1494T and m.A1555G. Four patients carried three unclassified mutations in GJB3 genes. Abstract only accessed.

PMID:25214170 - Beck et al. 2015; screened 188 HL probands in a 3 step process with GJB2 first, then GJB1, GJB3 and GJB6 and then if tested negative or heterozygote, testing of GJA1, GJB4, SLC26A4 and PJVK. 3 amino acid changes, c.166A>C, Lys56Gln (2/188), c.302G>A, Arg101Gln (1/188) and c.317G>A, Arg106His (1/188) were detected in the patient cohort but not in controls. The authors report that the role of these sequence variations remains unclear as no second mutation was found to establish a causative connection between genotype and phenotype.

PMID: 27610647 - Chen et al 2016 - using NGS they screened GJB2, SLC26A4, and GJB3, as well as exons of 57 additional candidate genes in 116 Chinese Han individuals suffering from hearing loss. 2 heterozygous variants were detected in GJB3 - c.131G>C, p.Trp44Ser; c.580G>A, p.Ala194Thr.

Biallelic cases:
PMID: 10587579 - Liu et al. (2000) - screened 25 Chinese families with recessive deafness and identified in two families affected individuals who were compound heterozygotes for Cx31 mutations. Both families had an in-frame 3 bp deletion (423-425delATT) in one allele, which leads to the loss of an isoleucine residue at codon 141, and a 423A>G transversion in the other allele, which creates an Ile>Val substitution (I141V) (later found to function as wild type by He et al 2005). Note: I think coords should be NM_001005752.1:c.421A>G and NM_001005752.1:c.421_423del.

Functional studies:
PMID: 16077902 - He et al 2005 - functional analysis of 11 disease-associated Cx31 (GJB3) variants, 2 which are associated with dominant HL (R180X, E183K) and 2 recessive HL (I141V, 141delI). R180X, E183K and 141delI were characterised by cytoplasmic accumulation of Cx31 and the absence of cell surface expression. I141V migrates mainly to the cell surface, which resembles that of WTCx31.; to: GJB3 - nonsyndromic genetic deafness association DISPUTED in ClinGen.

A large number of early studies have looked at GJB3 variants in HL patients. In all cases targeted screening of hearing loss genes was performed, with only a few genes looked at in most cases. At least 17 protein altering variants have been reported, but with no or limited segregation data. Two variants (NM_001005752.1:c.94C>T, Arg32Trp and c.598G>A, Val200Ile) are found at high allele frequency in the general population (both >0.02 gnomad v3.1) and c.529T>G, Tyr177Asp at a fairly high frequency (0.005535). 14 other variants are either not present in gnomad, or found at low frequency (< 0.0005). There is some data to support a functional change in proteins with 5 of the variants but no animal knockout model has been reported. One variant ((Ile141Val) found in a compound het case (Lui et al 2000) was found to migrate in to the cell surface in a similar way to wild type protein.

Monoallelic cases:
PMID:9843210 - Xia et al. 1998 - report monallelic variants found in GJB3 in 2 families with sensorineural deafness. Only the GJB3 gene was sequenced. In both families some carriers were unaffected. The two variants are ENST00000373362.3:c.547G>A GLU183LYS, ENST00000373362.3:c.538C>T (ARG180TER).

PMID:12630965 - Mhatre et al. 2003 - assessed 63 individuals with non-syndromic sporadic hearing impairment for CX31 (GJB3) mutations. 15 out of 63 patients (24%) had variants but only one variant was protein altering (C94T, R32W). This was found in two unrelated individuals with late onset hearing loss.

PMID: 10790215 - López-Bigas et al 2000 - report the molecular analysis of GJB3 in 153 patients with deafness and 110 with peripheral neuropathy. Identified two amino acid changes in patients; R32W and V200I. However, the R32W change was also detected in 18% of control subjects.

PMID:12791041 - Uyguner et al. 2003; Screened 60 Turkish patients with autosomal‐recessive NSSHL for variants in GJB2, GJB3, GJA1, DeltaGJB6-D13S1830 and CLDN14. A novel heterozygous variant, C667A;P223T, in GJB3 was found in a family with two affected children. However, the non-affected father also carried this variant. The authors suggest they may carry a second non-identified variant in a functionally related gene.

PMID:15131355 - Alexandrino et al. 2004 - analysed the GJB3 gene in 67 families with sporadic nonsyndromic hearing impairment. They found three amino acid changes: Y177D (c.529T > G), 49delK (c.144-146delGAA), and R32W (c.1227C > T). Abstract only accessed.

PMID:17259707 - Yang et al. 2007 - screened 260 Taiwanese individuals with nonsyndromic deafness and 120 with normal hearing. 8 genes were looked at GJB2, GJE1, GJB6, GJB4, GJB3, GJB1, GJA1 and pseudogene rho GJA1. A novel variant was identified GJB3 in 3 patients with nonsyndromic deafness. Abstract only accessed.

PMID:19744334 - Yuan et al. 2009 - screened 284 unrelated school children with hearing loss, and 200 control patients for variants in GJB2, GJB3, GJB6, SLC26A4, 12S rRNA, and tRNAser(UCN) genes. 2 patients were found with heterozygous protein altering variants that were not found in controls; c.24_49ins26bp (results in frameshift), c.497A>G, N166S. However, the patient carrying N166S mutation in one allele was verified to carry GJB2 235delC mutation in the other. Parental DNA was not available for the patient with the c.24_49ins26bp variant.

PMID:22617145 - Oh et al. 2013 - looked at GJB3 and GJB6 in 215 unrelated Korean nonsyndromic sensorineural HL patients. 7 variants were identified in GJB3. 2 variants (c.79G>A,p.V27M and c.250G>A,p.V84I) were not observed in normal Korean controls. Functional tests showed that these two variants did not functional normally when each was expressed as a heterozygote with the wild-type Cx31.

PMID: 23638949 - Yao et al 2013 - screened 227 segregating deaf students and 200 individuals with normal hearing for variants in GJB2, GJB3, SLC26A4, and mtDNA m.C1494T and m.A1555G. Four patients carried three unclassified mutations in GJB3 genes. Abstract only accessed.

PMID:25214170 - Beck et al. 2015; screened 188 HL probands in a 3 step process with GJB2 first, then GJB1, GJB3 and GJB6 and then if tested negative or heterozygote, testing of GJA1, GJB4, SLC26A4 and PJVK. 3 amino acid changes, c.166A>C, Lys56Gln (2/188), c.302G>A, Arg101Gln (1/188) and c.317G>A, Arg106His (1/188) were detected in the patient cohort but not in controls. The authors report that the role of these sequence variations remains unclear as no second mutation was found to establish a causative connection between genotype and phenotype.

PMID: 27610647 - Chen et al 2016 - using NGS they screened GJB2, SLC26A4, and GJB3, as well as exons of 57 additional candidate genes in 116 Chinese Han individuals suffering from hearing loss. 2 heterozygous variants were detected in GJB3 - c.131G>C, p.Trp44Ser; c.580G>A, p.Ala194Thr.

Biallelic cases:
PMID: 10587579 - Liu et al. (2000) - screened 25 Chinese families with recessive deafness and identified in two families affected individuals who were compound heterozygotes for Cx31 mutations. Both families had an in-frame 3 bp deletion (423-425delATT) in one allele, which leads to the loss of an isoleucine residue at codon 141, and a 423A>G transversion in the other allele, which creates an Ile>Val substitution (I141V) (later found to function as wild type by He et al 2005). Note: I think coords should be NM_001005752.1:c.421A>G and NM_001005752.1:c.421_423del.

Functional studies:
PMID: 16077902 - He et al 2005 - functional analysis of 11 disease-associated Cx31 (GJB3) variants, 2 which are associated with dominant HL (R180X, E183K) and 2 recessive HL (I141V, 141delI). R180X, E183K and 141delI were characterised by cytoplasmic accumulation of Cx31 and the absence of cell surface expression. I141V migrates mainly to the cell surface, which resembles that of WT Cx31.
Monogenic hearing loss v2.144 GJB3 Eleanor Williams changed review comment from: GJB3 - nonsyndromic genetic deafness association DISPUTED in ClinGen.

A large number of early studies have looked at GJB3 variants in HL patients. In all cases targeted screening of hearing loss genes was performed, with only a few genes looked at in many cases. At least 17 protein altering variants have been reported, but with no or limited segregation data. Two variants (NM_001005752.1:c.94C>T, Arg32Trp and c.598G>A, Val200Ile) are found at high allele frequency in the general population (both >0.02 gnomad v3.1) and c.529T>G, Tyr177Asp at a fairly high frequency (0.005535) . 14 other variants are either not present in gnomad, or found at low frequency (< 0.0005). There is some data to support a functional change in proteins with 5 of the variants but no animal knockout model has been reported. One variant ((Ile141Val) found in a compound het case (Lui et al 2000) was found to migrate in cell

Monoallelic cases:
PMID:9843210 - Xia et al. 1998 - report monallelic variants found in GJB3 in 2 families with sensorineural deafness. Only the GJB3 gene was sequenced. In both families some carriers were unaffected. The two variants are ENST00000373362.3:c.547G>A GLU183LYS, ENST00000373362.3:c.538C>T (ARG180TER).

PMID:12630965 - Mhatre et al. 2003 - assessed 63 individuals with non-syndromic sporadic hearing impairment for CX31 (GJB3) mutations. 15 out of 63 patients (24%) had variants but only one variant was protein altering (C94T, R32W). This was found in two unrelated individuals with late onset hearing loss.

PMID: 10790215 - López-Bigas et al 2000 - report the molecular analysis of GJB3 in 153 patients with deafness and 110 with peripheral neuropathy. Identified two amino acid changes in patients; R32W and V200I. However, the R32W change was also detected in 18% of control subjects.

PMID:12791041 - Uyguner et al. 2003; Screened 60 Turkish patients with autosomal‐recessive NSSHL for variants in GJB2, GJB3, GJA1, DeltaGJB6-D13S1830 and CLDN14. A novel heterozygous variant, C667A;P223T, in GJB3 was found in a family with two affected children. However, the non-affected father also carried this variant. The authors suggest they may carry a second non-identified variant in a functionally related gene.

PMID:15131355 - Alexandrino et al. 2004 - analysed the GJB3 gene in 67 families with sporadic nonsyndromic hearing impairment. They found three amino acid changes: Y177D (c.529T > G), 49delK (c.144-146delGAA), and R32W (c.1227C > T). Abstract only accessed.

PMID:17259707 - Yang et al. 2007 - screened 260 Taiwanese individuals with nonsyndromic deafness and 120 with normal hearing. 8 genes were looked at GJB2, GJE1, GJB6, GJB4, GJB3, GJB1, GJA1 and pseudogene rho GJA1. A novel variant was identified GJB3 in 3 patients with nonsyndromic deafness. Abstract only accessed.

PMID:19744334 - Yuan et al. 2009 - screened 284 unrelated school children with hearing loss, and 200 control patients for variants in GJB2, GJB3, GJB6, SLC26A4, 12S rRNA, and tRNAser(UCN) genes. 2 patients were found with heterozygous protein altering variants that were not found in controls; c.24_49ins26bp (results in frameshift), c.497A>G, N166S. However, the patient carrying N166S mutation in one allele was verified to carry GJB2 235delC mutation in the other. Parental DNA was not available for the patient with the c.24_49ins26bp variant.

PMID:22617145 - Oh et al. 2013 - looked at GJB3 and GJB6 in 215 unrelated Korean nonsyndromic sensorineural HL patients. 7 variants were identified in GJB3. 2 variants (c.79G>A,p.V27M and c.250G>A,p.V84I) were not observed in normal Korean controls. Functional tests showed that these two variants did not functional normally when each was expressed as a heterozygote with the wild-type Cx31.

PMID: 23638949 - Yao et al 2013 - screened 227 segregating deaf students and 200 individuals with normal hearing for variants in GJB2, GJB3, SLC26A4, and mtDNA m.C1494T and m.A1555G. Four patients carried three unclassified mutations in GJB3 genes. Abstract only accessed.

PMID:25214170 - Beck et al. 2015; screened 188 HL probands in a 3 step process with GJB2 first, then GJB1, GJB3 and GJB6 and then if tested negative or heterozygote, testing of GJA1, GJB4, SLC26A4 and PJVK. 3 amino acid changes, c.166A>C, Lys56Gln (2/188), c.302G>A, Arg101Gln (1/188) and c.317G>A, Arg106His (1/188) were detected in the patient cohort but not in controls. The authors report that the role of these sequence variations remains unclear as no second mutation was found to establish a causative connection between genotype and phenotype.

PMID: 27610647 - Chen et al 2016 - using NGS they screened GJB2, SLC26A4, and GJB3, as well as exons of 57 additional candidate genes in 116 Chinese Han individuals suffering from hearing loss. 2 heterozygous variants were detected in GJB3 - c.131G>C, p.Trp44Ser; c.580G>A, p.Ala194Thr.

Biallelic cases:
PMID: 10587579 - Liu et al. (2000) - screened 25 Chinese families with recessive deafness and identified in two families affected individuals who were compound heterozygotes for Cx31 mutations. Both families had an in-frame 3 bp deletion (423-425delATT) in one allele, which leads to the loss of an isoleucine residue at codon 141, and a 423A>G transversion in the other allele, which creates an Ile>Val substitution (I141V) (later found to function as wild type by He et al 2005). Note: I think coords should be NM_001005752.1:c.421A>G and NM_001005752.1:c.421_423del.

Functional studies:
PMID: 16077902 - He et al 2005 - functional analysis of 11 disease-associated Cx31 (GJB3) variants, 2 which are associated with dominant HL (R180X, E183K) and 2 recessive HL (I141V, 141delI). R180X, E183K and 141delI were characterised by cytoplasmic accumulation of Cx31 and the absence of cell surface expression. I141V migrates mainly to the cell surface, which resembles that of WTCx31.; to: GJB3 - nonsyndromic genetic deafness association DISPUTED in ClinGen.

A large number of early studies have looked at GJB3 variants in HL patients. In all cases targeted screening of hearing loss genes was performed, with only a few genes looked at in most cases. At least 17 protein altering variants have been reported, but with no or limited segregation data. Two variants (NM_001005752.1:c.94C>T, Arg32Trp and c.598G>A, Val200Ile) are found at high allele frequency in the general population (both >0.02 gnomad v3.1) and c.529T>G, Tyr177Asp at a fairly high frequency (0.005535). 14 other variants are either not present in gnomad, or found at low frequency (< 0.0005). There is some data to support a functional change in proteins with 5 of the variants but no animal knockout model has been reported. One variant ((Ile141Val) found in a compound het case (Lui et al 2000) was found to migrate in cell

Monoallelic cases:
PMID:9843210 - Xia et al. 1998 - report monallelic variants found in GJB3 in 2 families with sensorineural deafness. Only the GJB3 gene was sequenced. In both families some carriers were unaffected. The two variants are ENST00000373362.3:c.547G>A GLU183LYS, ENST00000373362.3:c.538C>T (ARG180TER).

PMID:12630965 - Mhatre et al. 2003 - assessed 63 individuals with non-syndromic sporadic hearing impairment for CX31 (GJB3) mutations. 15 out of 63 patients (24%) had variants but only one variant was protein altering (C94T, R32W). This was found in two unrelated individuals with late onset hearing loss.

PMID: 10790215 - López-Bigas et al 2000 - report the molecular analysis of GJB3 in 153 patients with deafness and 110 with peripheral neuropathy. Identified two amino acid changes in patients; R32W and V200I. However, the R32W change was also detected in 18% of control subjects.

PMID:12791041 - Uyguner et al. 2003; Screened 60 Turkish patients with autosomal‐recessive NSSHL for variants in GJB2, GJB3, GJA1, DeltaGJB6-D13S1830 and CLDN14. A novel heterozygous variant, C667A;P223T, in GJB3 was found in a family with two affected children. However, the non-affected father also carried this variant. The authors suggest they may carry a second non-identified variant in a functionally related gene.

PMID:15131355 - Alexandrino et al. 2004 - analysed the GJB3 gene in 67 families with sporadic nonsyndromic hearing impairment. They found three amino acid changes: Y177D (c.529T > G), 49delK (c.144-146delGAA), and R32W (c.1227C > T). Abstract only accessed.

PMID:17259707 - Yang et al. 2007 - screened 260 Taiwanese individuals with nonsyndromic deafness and 120 with normal hearing. 8 genes were looked at GJB2, GJE1, GJB6, GJB4, GJB3, GJB1, GJA1 and pseudogene rho GJA1. A novel variant was identified GJB3 in 3 patients with nonsyndromic deafness. Abstract only accessed.

PMID:19744334 - Yuan et al. 2009 - screened 284 unrelated school children with hearing loss, and 200 control patients for variants in GJB2, GJB3, GJB6, SLC26A4, 12S rRNA, and tRNAser(UCN) genes. 2 patients were found with heterozygous protein altering variants that were not found in controls; c.24_49ins26bp (results in frameshift), c.497A>G, N166S. However, the patient carrying N166S mutation in one allele was verified to carry GJB2 235delC mutation in the other. Parental DNA was not available for the patient with the c.24_49ins26bp variant.

PMID:22617145 - Oh et al. 2013 - looked at GJB3 and GJB6 in 215 unrelated Korean nonsyndromic sensorineural HL patients. 7 variants were identified in GJB3. 2 variants (c.79G>A,p.V27M and c.250G>A,p.V84I) were not observed in normal Korean controls. Functional tests showed that these two variants did not functional normally when each was expressed as a heterozygote with the wild-type Cx31.

PMID: 23638949 - Yao et al 2013 - screened 227 segregating deaf students and 200 individuals with normal hearing for variants in GJB2, GJB3, SLC26A4, and mtDNA m.C1494T and m.A1555G. Four patients carried three unclassified mutations in GJB3 genes. Abstract only accessed.

PMID:25214170 - Beck et al. 2015; screened 188 HL probands in a 3 step process with GJB2 first, then GJB1, GJB3 and GJB6 and then if tested negative or heterozygote, testing of GJA1, GJB4, SLC26A4 and PJVK. 3 amino acid changes, c.166A>C, Lys56Gln (2/188), c.302G>A, Arg101Gln (1/188) and c.317G>A, Arg106His (1/188) were detected in the patient cohort but not in controls. The authors report that the role of these sequence variations remains unclear as no second mutation was found to establish a causative connection between genotype and phenotype.

PMID: 27610647 - Chen et al 2016 - using NGS they screened GJB2, SLC26A4, and GJB3, as well as exons of 57 additional candidate genes in 116 Chinese Han individuals suffering from hearing loss. 2 heterozygous variants were detected in GJB3 - c.131G>C, p.Trp44Ser; c.580G>A, p.Ala194Thr.

Biallelic cases:
PMID: 10587579 - Liu et al. (2000) - screened 25 Chinese families with recessive deafness and identified in two families affected individuals who were compound heterozygotes for Cx31 mutations. Both families had an in-frame 3 bp deletion (423-425delATT) in one allele, which leads to the loss of an isoleucine residue at codon 141, and a 423A>G transversion in the other allele, which creates an Ile>Val substitution (I141V) (later found to function as wild type by He et al 2005). Note: I think coords should be NM_001005752.1:c.421A>G and NM_001005752.1:c.421_423del.

Functional studies:
PMID: 16077902 - He et al 2005 - functional analysis of 11 disease-associated Cx31 (GJB3) variants, 2 which are associated with dominant HL (R180X, E183K) and 2 recessive HL (I141V, 141delI). R180X, E183K and 141delI were characterised by cytoplasmic accumulation of Cx31 and the absence of cell surface expression. I141V migrates mainly to the cell surface, which resembles that of WTCx31.
Monogenic hearing loss v2.144 CEP250 Ivone Leong Classified gene: CEP250 as Amber List (moderate evidence)
Monogenic hearing loss v2.144 CEP250 Ivone Leong Gene: cep250 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.143 CEP250 Ivone Leong gene: CEP250 was added
gene: CEP250 was added to Hearing loss. Sources: Literature
for-review tags were added to gene: CEP250.
Mode of inheritance for gene: CEP250 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP250 were set to 24780881; 29718797; 30459346
Phenotypes for gene: CEP250 were set to Cone-rod dystrophy and hearing loss 2, OMIM:618358, MONDO:0020780
Review for gene: CEP250 was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be made considered for Green status at the next review.

This gene is also on the Retinal disorders panel (v2.58) with the following review from Zornitza Stark:
"Cone-rod dystrophy and hearing loss-2 (CRDHL2) is characterized by retinal dystrophy, with photophobia and progressive reduction in visual acuity, associated with sensorineural hearing loss. Three unrelated families reported.
Zornitza Stark (Australian Genomics), 10 Oct 2020"
Sources: Literature
Monogenic hearing loss v2.142 KCNMA1 Arina Puzriakova Classified gene: KCNMA1 as Red List (low evidence)
Monogenic hearing loss v2.142 KCNMA1 Arina Puzriakova Added comment: Comment on list classification: Multiple individuals with KCNMA1-related channelopathy characterised by a variety of neurologic symptoms, with both mono- and biallelic cases reported. Only a single patient described by Liang et al., 2019 (PMID: 31152168) with hearing impairment and therefore a Red rating on this panel is appropriate.
Monogenic hearing loss v2.142 KCNMA1 Arina Puzriakova Gene: kcnma1 has been classified as Red List (Low Evidence).
Monogenic hearing loss v2.141 KCNMA1 Arina Puzriakova Publications for gene: KCNMA1 were set to
Monogenic hearing loss v2.140 KCNMA1 Arina Puzriakova Mode of inheritance for gene: KCNMA1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.139 GJB3 Eleanor Williams edited their review of gene: GJB3: Changed publications: 9843210, 12630965, 10790215, 12791041, 15131355, 17259707, 19744334, 22617145, 23638949, 25214170, 27610647, 10587579, 16077902
Monogenic hearing loss v2.139 GJB3 Eleanor Williams edited their review of gene: GJB3: Changed publications: 9843210, 12630965, 10790215, 12791041, 15131355, 17259707, 19744334, 22617145, 23638949, 25214170, 27610647, 10587579, 1607790279
Monogenic hearing loss v2.139 GJB3 Eleanor Williams reviewed gene: GJB3: Rating: AMBER; Mode of pathogenicity: None; Publications: 9843210, 12630965, 10790215, 12791041, 15131355, 17259707, 19744334, 22617145, 23638949, 25214170, 27610647, 105875, 1607790279; Phenotypes: Deafness, autosomal dominant 2B OMIM:612644; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.139 GJB6 Eleanor Williams commented on gene: GJB6: As reviewer Zornitza Stark reports this gene has Refuted status in association with hearing loss by ClinGen. However, leaving as amber, as there is still some evidence to support the possibility that SNV in this gene are associated with hearing loss (Grifa et al and Amritkumar et al).
Monogenic hearing loss v2.139 PMP22 Eleanor Williams Classified gene: PMP22 as Amber List (moderate evidence)
Monogenic hearing loss v2.139 PMP22 Eleanor Williams Added comment: Comment on list classification: After consultation with Genomics England clinical team leaving this gene as amber as the majority of patients do not have a hearing loss phenotype, and there are also issues around the potential predictive nature of the neurological aspects if this panel was applied to a paediatric hearing loss cohort.
Monogenic hearing loss v2.139 PMP22 Eleanor Williams Gene: pmp22 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.138 SCD5 Eleanor Williams Classified gene: SCD5 as Red List (low evidence)
Monogenic hearing loss v2.138 SCD5 Eleanor Williams Added comment: Comment on list classification: Changing rating from grey to red. As outlined by the reviewer, one large Chinese family with autosomal dominant non syndromic hearing loss reported, in which a missense variant in the SCD5 gene (c.626G > C, p.W209S, NM_ 001037582) segregated perfectly cases with hearing loss.
Monogenic hearing loss v2.138 SCD5 Eleanor Williams Gene: scd5 has been classified as Red List (Low Evidence).
Monogenic hearing loss v2.137 SCD5 Eleanor Williams Phenotypes for gene: SCD5 were changed from Deafness, autosomal dominant 79, MIM#619086 to Deafness, autosomal dominant 79 OMIM:619086; deafness, autosomal dominant 79 MONDO:0033668
Monogenic hearing loss v2.136 COG4 Ivone Leong Classified gene: COG4 as Amber List (moderate evidence)
Monogenic hearing loss v2.136 COG4 Ivone Leong Gene: cog4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.135 COG4 Ivone Leong gene: COG4 was added
gene: COG4 was added to Hearing loss. Sources: Literature
for-review tags were added to gene: COG4.
Mode of inheritance for gene: COG4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COG4 were set to 31949312; 30290151
Phenotypes for gene: COG4 were set to Saul-Wilson syndrome, OMIM:618150; microcephalic osteodysplastic dysplasia, Saul-Wilson type, MONDO:0019407
Mode of pathogenicity for gene: COG4 was set to Other
Review for gene: COG4 was set to AMBER
Added comment: This gene is associated with a phenotype in OMIM and Gene2Phenotype. This gene was added to the Cataracts panel by Zornitza Stark (Australian Genomics).

"Saul-Wilson syndrome (AD): 14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like) All have a recurrent de novo heterozygous missense variant (p.Gly516Arg). Please note bi-allelic variants cause CDG. Sources: Expert list
Zornitza Stark (Australian Genomics), 7 Jul 2020"

PMID: 30290151, many of the affected patients also have hearing loss and the authors suggest that the Saul-Wilson syndrome variant is gain of function. Therefore, this gene should be considered to be Green at the next review.
Sources: Literature
Monogenic hearing loss v2.134 SCD5 Zornitza Stark gene: SCD5 was added
gene: SCD5 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: SCD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCD5 were set to 31972369
Phenotypes for gene: SCD5 were set to Deafness, autosomal dominant 79, MIM#619086
Review for gene: SCD5 was set to RED
Added comment: Single 5-generation family reported with a missense variant segregating in 19 affected individuals. Variant is found at a low frequency in ExAC.
Sources: Literature
Monogenic hearing loss v2.134 MORC2 Arina Puzriakova Classified gene: MORC2 as Amber List (moderate evidence)
Monogenic hearing loss v2.134 MORC2 Arina Puzriakova Added comment: Comment on list classification: Though signs suggestive of neuropathy were observed in the cohort presented by Sacoto et al (PMID:32693025), these were not the predominant feature of the disease presentation or the primary indication for diagnostic testing. Furthermore, some cases with hearing loss would not be tested for other panels related to this phenotype (e.g. ID, severe microcephaly) as they did not exhibit the relevant features.

Therefore, this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag).
Monogenic hearing loss v2.134 MORC2 Arina Puzriakova Gene: morc2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.133 MORC2 Arina Puzriakova Phenotypes for gene: MORC2 were changed from Developmental delay; Intellectual disability; Growth retardation; Microcephaly; Craniofacial dysmorphism; Charcot-Marie-Tooth disease, axonal, type 2Z, OMIM:616688 to Sensorineural hearing loss; Developmental delay; Intellectual disability; Growth retardation; Microcephaly; Craniofacial dysmorphism; Charcot-Marie-Tooth disease, axonal, type 2Z, OMIM:616688
Monogenic hearing loss v2.132 MORC2 Arina Puzriakova gene: MORC2 was added
gene: MORC2 was added to Hearing loss. Sources: Literature
for-review tags were added to gene: MORC2.
Mode of inheritance for gene: MORC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MORC2 were set to 32693025
Phenotypes for gene: MORC2 were set to Developmental delay; Intellectual disability; Growth retardation; Microcephaly; Craniofacial dysmorphism; Charcot-Marie-Tooth disease, axonal, type 2Z, OMIM:616688
Review for gene: MORC2 was set to GREEN
Added comment: MORC2 variants have commonly been associated with CMT, presenting axonal neuropathy with progressive weakness, muscle cramps and sensory impairment. However, Sacoto et al (2020) (PMID: 32693025) present a cohort of 20 individuals (19 kindreds) with a neurodevelopmental disorder characterised by DD, ID (18/20 - mild to severe), short stature (18/20), microcephaly (15/20) and variable craniofacial dysmorphisms. Hearing loss was observed in 11/19 subjects, primarily SNHL.
Sources: Literature
Monogenic hearing loss v2.131 MET Eleanor Williams Classified gene: MET as Amber List (moderate evidence)
Monogenic hearing loss v2.131 MET Eleanor Williams Added comment: Comment on list classification: Promoting this gene to amber as two cases reported, with segregation data.
Monogenic hearing loss v2.131 MET Eleanor Williams Gene: met has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.130 MET Eleanor Williams gene: MET was added
gene: MET was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: MET was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MET were set to 25941349; 27717089
Phenotypes for gene: MET were set to Deafness, autosomal recessive 97 OMIM:616705; autosomal recessive nonsyndromic deafness 97 MONDO:0014739
Review for gene: MET was set to AMBER
Added comment: Gene suggested by Professor Sadaf Naz, PhD, School of Biological Sciences, University of the Punjab, Pakistan

Provisionally associated with ?Deafness, autosomal recessive 97 MIM#616705 in OMIM. 2 cases reported:

PMID: 25941349 - Mujtaba et al 2015 - report a large consanguineous Pakistani family with some members affected by hearing loss. They identified, through genome-wide homozygosity mapping and then whole exome sequencing, a homozygous missense variant located in MET (NM_000245.2), c.2521T>G (p.F841V) that segregates with hearing loss in 9 affected individuals.

PMID: 27717089 - Alabdullatif et al 2017 - from a review of clinical and molecular data for 227 individuals from a highly consanguineous population who underwent a combined (CGH+SNP) CMA test, they report 2 brothers with hearing loss and arthrogryposis in which a homozygous variant c.3557T>G (p.F1186C) in MET was identified through WES after a region of homozygosity was identified. The first cousin parents were both heterozygous for this variant. They suggest that the arthrogryposis could be a variable feature of the disease or be caused by a second recessive disease not detected in this study.
Sources: Expert list
Monogenic hearing loss v2.129 PMP22 Eleanor Williams Classified gene: PMP22 as Amber List (moderate evidence)
Monogenic hearing loss v2.129 PMP22 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber. Three independent cases reported in which patients have Charcot-Marie-Tooth disease plus hearing loss and variants in PMP22, but waiting for feedback from Genomics England clinical team as to whether this gene is appropriate to be green as HL is part of a syndrome of features.
Monogenic hearing loss v2.129 PMP22 Eleanor Williams Gene: pmp22 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.128 PMP22 Eleanor Williams Phenotypes for gene: PMP22 were changed from to Charcot-Marie-Tooth disease, type 1E OMIM:118300; Charcot-Marie-Tooth disease type 1E MONDO:0007311
Monogenic hearing loss v2.127 PMP22 Eleanor Williams Publications for gene: PMP22 were set to
Monogenic hearing loss v2.126 PMP22 Eleanor Williams Mode of inheritance for gene: PMP22 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v2.125 PMP22 Eleanor Williams changed review comment from: Associated with Charcot-Marie-Tooth disease, type 1E #118300 (AD) in which hearing loss is listed as a clinical feature

PMID: 12578939 - Sambuughin et al 2003 - report deafness associated with a demyelinating neuropathy in three individuals of a family in whom a novel 12bp deletion resulting in the deletion of four-amino acid deletion (115-118) in the PMP22 gene was identified (targeted sequencing of PMP22). No asymptomatic family members had the deletion nor was it detected in 55 healthy controls.

PMID: 11835375 - Boerkoel et al 2002 - screened PMP22, GJB1, and MPZ contained 159 unrelated patients with primary peripheral demyelinating neuropathy or a primary peripheral axonal neuropathy and report 5 which have heterozygous variants in PMP22, 1 of which had a clinical diagnosis of CMT1 + deafness (variant 82T>C W28R). An affected sibling had the same variant.

PMID: 10330345 - Kovach et al 1999 - analysis of a 7 generation family from central Illinois with autosomal dominant CMT and deafness. In the 31 affected family members, hearing loss ranged from borderline normal to profound hearing loss, with all having at least mild bilateral hearing loss by adulthood. Following haplotype analysis they sequenced PMP22 and a point mutation was found in affected individuals G->C at position 248 in exon 4 in the heterozygous state (p.Ala67Pro).

PMID: 8355122 - Hamiel et al 1993 - Abstract only accessed. Describe a family with hereditary motor-sensory neuropathy with sensorineural deafness is described; the neurologic features and deafness were apparent in early childhood and infancy.

Summary: 3 cases in which hearing loss is reported in CMT patients with PMP22 variants. In all cases a limited number of genes were sequenced.; to: Associated with Charcot-Marie-Tooth disease, type 1E #118300 (AD) in which hearing loss is listed as a clinical feature

PMID: 12578939 - Sambuughin et al 2003 - report deafness associated with a demyelinating neuropathy in three individuals of a family in whom a novel 12bp deletion resulting in the deletion of four-amino acid deletion (115-118) in the PMP22 gene was identified (targeted sequencing of PMP22). No asymptomatic family members had the deletion nor was it detected in 55 healthy controls.

PMID: 11835375 - Boerkoel et al 2002 - screened PMP22, GJB1, and MPZ in 159 unrelated patients with primary peripheral demyelinating neuropathy or a primary peripheral axonal neuropathy and report 5 which have heterozygous variants in PMP22, 1 of which had a clinical diagnosis of CMT1 + deafness (variant 82T>C W28R). An affected sibling had the same variant.

PMID: 10330345 - Kovach et al 1999 - analysis of a 7 generation family from central Illinois with autosomal dominant CMT and deafness. In the 31 affected family members, hearing loss ranged from borderline normal to profound hearing loss, with all having at least mild bilateral hearing loss by adulthood. Following haplotype analysis they sequenced PMP22 and a point mutation was found in affected individuals G->C at position 248 in exon 4 in the heterozygous state (p.Ala67Pro).

PMID: 8355122 - Hamiel et al 1993 - Abstract only accessed. Describe a family with hereditary motor-sensory neuropathy with sensorineural deafness is described; the neurologic features and deafness were apparent in early childhood and infancy.

Summary: 3 cases in which hearing loss is reported in CMT patients with PMP22 variants. In all cases a limited number of genes were sequenced.
Monogenic hearing loss v2.125 COCH Eleanor Williams Added comment: Comment on mode of inheritance: Leaving mode of inheritance as Monoallelic only for now, but with recommendation that it should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next GMS review.
Monogenic hearing loss v2.125 COCH Eleanor Williams Mode of inheritance for gene: COCH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v2.124 COCH Eleanor Williams edited their review of gene: COCH: Changed publications: 29449721, 31126177, 32562050, 32939038
Monogenic hearing loss v2.124 COCH Eleanor Williams edited their review of gene: COCH: Changed publications: 31126177
Monogenic hearing loss v2.124 COCH Eleanor Williams Publications for gene: COCH were set to PMID: 10400989; 11332404; 11709536; 12928864; 14512963; 16078052; 16261627; 16481359; 18312449; 19161137; 20097680; 22139968; 23684986; 7829101; 8817345; 9441737; 9806553; 9931344
Monogenic hearing loss v2.123 COCH Eleanor Williams Phenotypes for gene: COCH were changed from hearing loss; #601369:Deafness, autosomal dominant 9; Nonsyndromic Hearing Loss, Dominant to Deafness, autosomal recessive 110 OMIM:618094; Deafness, autosomal dominant 9 OMIM:601369; deafness, autosomal recessive 110 MONDO:0054860; autosomal dominant nonsyndromic deafness 9 MONDO:0011058
Monogenic hearing loss v2.122 COCH Eleanor Williams Tag for-review tag was added to gene: COCH.
Monogenic hearing loss v2.122 COCH Eleanor Williams reviewed gene: COCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 29449721, 29449721, 31126177, 32562050; Phenotypes: Deafness, autosomal recessive 110 OMIM:618094, Deafness, autosomal dominant 9 OMIM:601369, deafness, autosomal recessive 110 MONDO:0054860, autosomal dominant nonsyndromic deafness 9 MONDO:0011058; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.122 THOC1 Eleanor Williams Phenotypes for gene: THOC1 were changed from Nonsyndromic hearing loss to Nonsyndromic hearing loss; nonsyndromic genetic deafness MONDO:0019497
Monogenic hearing loss v2.121 THOC1 Eleanor Williams Classified gene: THOC1 as Amber List (moderate evidence)
Monogenic hearing loss v2.121 THOC1 Eleanor Williams Added comment: Comment on list classification: Following review from Zornitza Stark changing the rating of THOC1 from grey to amber as there is one large family plus functional data to support the proposal that a variant in THOC1 is associated with hearing loss.
Monogenic hearing loss v2.121 THOC1 Eleanor Williams Gene: thoc1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.120 LMX1A Eleanor Williams Tag watchlist tag was added to gene: LMX1A.
Tag for-review tag was added to gene: LMX1A.
Monogenic hearing loss v2.120 LMX1A Eleanor Williams Classified gene: LMX1A as Amber List (moderate evidence)
Monogenic hearing loss v2.120 LMX1A Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber but with a recommendation for a green rating following GMS review.
Monogenic hearing loss v2.120 LMX1A Eleanor Williams Gene: lmx1a has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.119 LMX1A Eleanor Williams Added comment: Comment on mode of inheritance: Setting MOI to Monoallelic as only one case of biallelic reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.
Monogenic hearing loss v2.119 LMX1A Eleanor Williams Mode of inheritance for gene: LMX1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.118 LMX1A Eleanor Williams Phenotypes for gene: LMX1A were changed from to Deafness, autosomal dominant 7 OMIM:601412; autosomal dominant nonsyndromic deafness 7 MONDO:0011074
Monogenic hearing loss v2.117 LMX1A Eleanor Williams Publications for gene: LMX1A were set to
Monogenic hearing loss v2.116 LMX1A Eleanor Williams edited their review of gene: LMX1A: Changed rating: GREEN; Changed publications: 29754270, 29971487, 32840933, 19540218, 18985389; Changed phenotypes: Deafness, autosomal dominant 7 OMIM:601412, autosomal dominant nonsyndromic deafness 7 MONDO:0011074; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.116 LMX1A Eleanor Williams commented on gene: LMX1A
Monogenic hearing loss v2.116 NARS2 Eleanor Williams changed review comment from: Comment on list classification: Changing the rating from red to amber for NARS2. Only one family with non-syndromic deafness, but several with deafness in conjunction with other clinical features.; to: Comment on list classification: Changing the rating from red to amber for NARS2. Only one family with non-syndromic deafness, but several with deafness in conjunction with other clinical features. This gene should be reviewed at the next major GMS update to decide whether it would be appropriate for the panel as a green gene.
Monogenic hearing loss v2.116 NARS2 Eleanor Williams Tag for-review tag was added to gene: NARS2.
Monogenic hearing loss v2.116 NARS2 Eleanor Williams Classified gene: NARS2 as Amber List (moderate evidence)
Monogenic hearing loss v2.116 NARS2 Eleanor Williams Added comment: Comment on list classification: Changing the rating from red to amber for NARS2. Only one family with non-syndromic deafness, but several with deafness in conjunction with other clinical features.
Monogenic hearing loss v2.116 NARS2 Eleanor Williams Gene: nars2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.115 NARS2 Eleanor Williams commented on gene: NARS2: PMID: 25807530 - Simon et al 2015 - report 2 unrelated families with 3 different variants in NARS2. One family is segregating nonsyndromic hearing loss (DFNB94) and another with Leigh syndrome. In the family with Leigh syndrome two affected children failed the newborn hearing test.

PMID: 28077841 - Mizuguchi et al 2017 - report 4 individuals from 3 families with homozygous or compound het variants in NARS2 found by WES. All had hearing impairment (detected <2 years of age) among other clinical features including seizures and hypotonia.

PMID: 30327238 - Seaver et al 2018 - report two infant brothers who presented with focal status epilepticus that progressed to lethal epileptic encephalopathy. Compound het missense variants found by WES in NARS2. The younger brother failed the newborn hearing screen.

PMID: 25385316 - Vanlander et al 2015 - report 2 siblings born to consanguineous parents in which a homozygous missense mutation (c.822G>C) was found in NARS2). One sibling had mild intellectual disability and epilepsy in childhood, whereas the other had severe myopathy. Hearing loss NOT reported.
Monogenic hearing loss v2.115 NARS2 Eleanor Williams Phenotypes for gene: NARS2 were changed from to Deafness, autosomal recessive 94 OMIM:618434; Combined oxidative phosphorylation deficiency 24 OMIM:616239; deafness, autosomal recessive 94 MONDO:0032749; combined oxidative phosphorylation defect type 24 MONDO:0014547
Monogenic hearing loss v2.114 NARS2 Eleanor Williams Publications for gene: NARS2 were set to 25807530
Monogenic hearing loss v2.113 MPZL2 Eleanor Williams Tag for-review tag was added to gene: MPZL2.
Monogenic hearing loss v2.113 MPZL2 Eleanor Williams Phenotypes for gene: MPZL2 were changed from Deafness, autosomal recessive 111, MIM#618145 to Deafness, autosomal recessive 111 OMIM:618145; deafness, autosomal recessive 111 MONDO:0029142
Monogenic hearing loss v2.112 MPZL2 Eleanor Williams Publications for gene: MPZL2 were set to 29982980; 29961571
Monogenic hearing loss v2.111 MPZL2 Eleanor Williams Classified gene: MPZL2 as Amber List (moderate evidence)
Monogenic hearing loss v2.111 MPZL2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber with a recommendation of a green rating following GMS review. 15 cases reported, 3 different variants. Mouse model supports role of gene in hearing loss.
Monogenic hearing loss v2.111 MPZL2 Eleanor Williams Gene: mpzl2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.110 MPZL2 Eleanor Williams edited their review of gene: MPZL2: Changed rating: GREEN
Monogenic hearing loss v2.110 MPZL2 Eleanor Williams edited their review of gene: MPZL2: Changed publications: 29982980, 29961571, 32203226
Monogenic hearing loss v2.110 MPZL2 Eleanor Williams reviewed gene: MPZL2: Rating: ; Mode of pathogenicity: None; Publications: 29982980, 29961571; Phenotypes: Deafness, autosomal recessive 111 OMIM:618145, deafness, autosomal recessive 111 MONDO:0029142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.110 PLS1 Eleanor Williams Tag for-review tag was added to gene: PLS1.
Monogenic hearing loss v2.110 PLS1 Eleanor Williams Phenotypes for gene: PLS1 were changed from Deafness to Deafness, autosomal dominant 76 OMIM:618787; deafness, autosomal dominant 76 MONDO:0032917
Monogenic hearing loss v2.109 PLS1 Eleanor Williams Classified gene: PLS1 as Amber List (moderate evidence)
Monogenic hearing loss v2.109 PLS1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber with a recommendation of green rating at the next GMS review.
Monogenic hearing loss v2.109 PLS1 Eleanor Williams Gene: pls1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.108 PLS1 Eleanor Williams edited their review of gene: PLS1: Changed rating: GREEN
Monogenic hearing loss v2.108 PLS1 Eleanor Williams edited their review of gene: PLS1: Changed publications: 31397523, 31432506, 30872814; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.108 PLS1 Eleanor Williams reviewed gene: PLS1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 76 OMIM:618787, deafness, autosomal dominant 76 MONDO:0032917; Mode of inheritance: None
Monogenic hearing loss v2.108 SPTBN4 Arina Puzriakova Classified gene: SPTBN4 as Amber List (moderate evidence)
Monogenic hearing loss v2.108 SPTBN4 Arina Puzriakova Added comment: Comment on list classification: Rating Amber as degree of the deafness phenotype is unclear in 2/4 individuals reported with auditory impairment. Animal model supports association with this presentation but additional congenital/early-onset cases required before inclusion on a diagnostic hearing loss panel (added 'watchlist' tag)
Monogenic hearing loss v2.108 SPTBN4 Arina Puzriakova Gene: sptbn4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.107 SPTBN4 Arina Puzriakova Tag watchlist tag was added to gene: SPTBN4.
Monogenic hearing loss v2.107 SPTBN4 Arina Puzriakova gene: SPTBN4 was added
gene: SPTBN4 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: SPTBN4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN4 were set to 28540413; 29861105; 31230720; 32672909
Phenotypes for gene: SPTBN4 were set to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, 617519
Review for gene: SPTBN4 was set to AMBER
Added comment: At least 11 individuals from 9 unrelated families with biallelic variants in SPTBN4 reported at present. Of these, two unrelated patients presented early-onset deafness (PMID:28540413, 31230720) and two further unrelated individuals displayed abnormal auditory brain stem responses consistent with auditory neuropathy but no further details regarding the deafness phenotype are provided (PMID:29861105). Furthermore, loss of Sptbn4 in mice causes deafness and auditory neuropathy.
Sources: Literature
Monogenic hearing loss v2.106 PPIP5K2 Eleanor Williams Classified gene: PPIP5K2 as Amber List (moderate evidence)
Monogenic hearing loss v2.106 PPIP5K2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber. 2 cases (but with same variant, likely founder effect) plus mouse model replicating disease.
Monogenic hearing loss v2.106 PPIP5K2 Eleanor Williams Gene: ppip5k2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.105 PPIP5K2 Eleanor Williams Phenotypes for gene: PPIP5K2 were changed from Deafness, autosomal recessive 100, MIM#618422 to Deafness, autosomal recessive 100, MIM#618422; deafness, autosomal recessive 100 MONDO:0032740
Monogenic hearing loss v2.104 PPIP5K2 Eleanor Williams edited their review of gene: PPIP5K2: Changed rating: AMBER; Changed publications: 29590114; Changed phenotypes: Deafness, autosomal recessive 100, 618422, deafness, autosomal recessive 100 MONDO:0032740; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.104 PPIP5K2 Eleanor Williams commented on gene: PPIP5K2
Monogenic hearing loss v2.104 ROR1 Eleanor Williams Phenotypes for gene: ROR1 were changed from Deafness, autosomal recessive 108, MIM#617654 to Deafness, autosomal recessive 108, MIM#617654; deafness, autosomal recessive 108 MONDO:0033200
Monogenic hearing loss v2.103 ROR1 Eleanor Williams Classified gene: ROR1 as Amber List (moderate evidence)
Monogenic hearing loss v2.103 ROR1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber as there is 1 familial case plus a mouse model that replicates the disease.
Monogenic hearing loss v2.103 ROR1 Eleanor Williams Gene: ror1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.102 ROR1 Eleanor Williams reviewed gene: ROR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27162350; Phenotypes: ?Deafness, autosomal recessive 108, 617654, deafness, autosomal recessive 108 MONDO:0033200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.102 SNAI2 Eleanor Williams Tag for-review tag was added to gene: SNAI2.
Monogenic hearing loss v2.102 SNAI2 Eleanor Williams Classified gene: SNAI2 as Green List (high evidence)
Monogenic hearing loss v2.102 SNAI2 Eleanor Williams Added comment: Comment on list classification: Leaving this gene as green for now, but it should be reviewed by the GMS due to the fact that only two cases have been reported of homozygous deletions in patients with Waardenburg syndrome, type 2D. Those reported with heterozygous variants either have no hearing loss or the variants have an allele frequency > 0.001 in the ExAC_EAS database.
Monogenic hearing loss v2.102 SNAI2 Eleanor Williams Gene: snai2 has been classified as Green List (High Evidence).
Monogenic hearing loss v2.101 SNAI2 Eleanor Williams changed review comment from: Associated with Waardenburg syndrome, type 2D #608890 (AR) in OMIM, and Waardenburg syndrome (MONDO_0018094) in ClinGen (limited, assessed in 2017). This syndrome is characterized by deafness and pigmentary abnormalities.
SNAI2 is also know has SLUG.

Some reports of heterozgous variants associated with piebaldism (PMID: 12955764, PMID: 24443330) but no hearing loss.

PMID: 30936914 - Li et al 2019 - screened 90 patients with WS by NGS and found 2 patients with WS type 2 with de novo SNAI2 variants (c.230C>G, p. S77C and c.365C>T, p.A122V), however these variants were found at a frequency >1/10000 in the Exac population database (0.0045 and 0.0015 respectively). Presume these variants are heterozygous as they are de novo.

PMID: 12444107 - Sanchez-Martin et al 2002 - screened 38 unrelated patients with features of WS for SLUG genomic rearrangements, deletions or point mutations and found two unrelated (Bangladeshi and Dutch origin) patients with WS2 that have homozygous deletions spanning the entire SLUG coding region.; to: Associated with Waardenburg syndrome, type 2D #608890 (AR) in OMIM, and Waardenburg syndrome (MONDO_0018094) in ClinGen (limited, assessed in 2017). This syndrome is characterized by deafness and pigmentary abnormalities.
SNAI2 is also know has SLUG.

Some reports of heterozygous variants associated with piebaldism (PMID: 12955764, PMID: 24443330) but no hearing loss.

PMID: 30936914 - Li et al 2019 - screened 90 patients with WS by NGS and found 2 patients with WS type 2 with de novo SNAI2 variants (c.230C>G, p. S77C and c.365C>T, p.A122V), however these variants were found at a frequency >1/10000 in the Exac population database (0.0045 and 0.0015 respectively). Presume these variants are heterozygous as they are de novo.

PMID: 12444107 - Sanchez-Martin et al 2002 - screened 38 unrelated patients with features of WS for SLUG genomic rearrangements, deletions or point mutations and found two unrelated (Bangladeshi and Dutch origin) patients with WS2 that have homozygous deletions spanning the entire SLUG coding region.
Monogenic hearing loss v2.101 SNAI2 Eleanor Williams edited their review of gene: SNAI2: Changed rating: AMBER; Changed publications: 30936914, 12444107; Changed phenotypes: Waardenburg syndrome, type 2D, Waardenburg syndrome type 2 MONDO_0019517; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.101 SNAI2 Eleanor Williams commented on gene: SNAI2
Monogenic hearing loss v2.101 SLITRK6 Eleanor Williams Tag for-review tag was added to gene: SLITRK6.
Monogenic hearing loss v2.101 SLITRK6 Eleanor Williams Classified gene: SLITRK6 as Amber List (moderate evidence)
Monogenic hearing loss v2.101 SLITRK6 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber but with a recommendation for a green rating following GMS review.
Monogenic hearing loss v2.101 SLITRK6 Eleanor Williams Gene: slitrk6 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.100 SLITRK6 Eleanor Williams Phenotypes for gene: SLITRK6 were changed from Deafness and myopia, 221200 to Deafness and myopia, 221200; high myopia-sensorineural deafness syndrome MONDO:0009082
Monogenic hearing loss v2.99 SLITRK6 Eleanor Williams Publications for gene: SLITRK6 were set to
Monogenic hearing loss v2.98 SLITRK6 Eleanor Williams edited their review of gene: SLITRK6: Changed rating: GREEN; Changed publications: 29551497, 23946138, 23543054; Changed phenotypes: Deafness and myopia, 221200, high myopia-sensorineural deafness syndrome MONDO:0009082; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.98 SLITRK6 Eleanor Williams changed review comment from: Associated with Deafness and myopia #221200 (AR) in OMIM.

PMID: 29551497 - Salime et al 2018 - report a consanguineous Moroccan family with 2 children diagnosed for deafness and myopia in infancy. The SLITRK6 was sequenced and a homozygous 1 bp deletion leading to a premature stop codon p.Trp232Cysfs*10 was found. The parents were heterozygous for the variant as were 3 unaffected siblings.

PMID: 23946138 - Morlet et al 2014 - report 9 Old Order Amish individuals who were homozygous for a nonsense mutation of SLITRK6 (c.1240C>T, p.Gln414Ter) and suffered progressive cochlear and auditory nerve dysfunction

PMID: 23543054 - Tekin et al 2013 - report 3 families (1 old-order Amish family, 1 consanguineous Turkish and 1 Greek).
The Amish and Turkish families had members with congenital myopia and prelingual sensorineural hearing loss, while the affected Greek family had hearing loss only. Homozygous nonsense variants were found in SLITRK6 in all 3 families (Amish p.Q414X, Turkish p.S297X, Greek p.R181X). WES was performed on the Turkish family, targeted sequencing in a region of autozygosity in the Amish family, and targeted SLITRK6 sequencing in the Greek family in which affected members had the same haplotype in that region. Mouse Slitrk6 KO show a hearing loss phenotype.

Summary: founder mutation in SLITRK6 in several Amish families, plus 3 other variants reported in families of other ethnicities.; to: Associated with Deafness and myopia #221200 (AR) in OMIM.

PMID: 29551497 - Salime et al 2018 - report a consanguineous Moroccan family with 2 children diagnosed for deafness and myopia in infancy. The SLITRK6 was sequenced and a homozygous 1 bp deletion leading to a premature stop codon p.Trp232Cysfs*10 was found. The parents were heterozygous for the variant as were 3 unaffected siblings.

PMID: 23946138 - Morlet et al 2014 - report 9 Old Order Amish individuals who were homozygous for a nonsense mutation of SLITRK6 (c.1240C>T, p.Gln414Ter) and suffered progressive cochlear and auditory nerve dysfunction

PMID: 23543054 - Tekin et al 2013 - report 3 families (1 old-order Amish family, 1 consanguineous Turkish and 1 Greek).
The Amish and Turkish families had members with congenital myopia and prelingual sensorineural hearing loss, while the affected Greek family had hearing loss only. Homozygous nonsense variants were found in SLITRK6 in all 3 families (Amish p.Q414X, Turkish p.S297X, Greek p.R181X). WES was performed on the Turkish family, targeted sequencing in a region of autozygosity in the Amish family, and targeted SLITRK6 sequencing in the Greek family in which affected members had the same haplotype in that region. Mouse Slitrk6 KO show a hearing loss phenotype.

Summary: founder mutation in SLITRK6 in several Amish families, plus 3 other variants reported in families of other ethnicities. Mouse model shows hearing loss phenotype.
Monogenic hearing loss v2.98 SLITRK6 Eleanor Williams commented on gene: SLITRK6
Monogenic hearing loss v2.98 SIX5 Eleanor Williams Classified gene: SIX5 as Red List (low evidence)
Monogenic hearing loss v2.98 SIX5 Eleanor Williams Added comment: Comment on list classification: Demoting from amber to red in view of ClinGen DISPUTED rating and no further reports of variants in SIX5 associated with hearing loss.
Monogenic hearing loss v2.98 SIX5 Eleanor Williams Gene: six5 has been classified as Red List (Low Evidence).
Monogenic hearing loss v2.97 EYA1 Eleanor Williams Publications for gene: EYA1 were set to PMID:10072433; 10471511; 10655545; 10991693; 11409867; 11703923; 11734542; 12404110; 14517553; 14628042; 14628052; 14628053; 15146463; 15226428; 15479196; 15493068; 16441263; 16691597; 16990542; 18177466; 18220287; 19206155; 19234442; 21280147; 2773990; 5365063; 9006082; 9020840; 9342347; 9359046; 9361030; 9603436
Monogenic hearing loss v2.96 EYA1 Eleanor Williams changed review comment from: PMID: 23840632 - Song et al 2013 - analysed EYA1, SIX1 and SIX5 in 7 families (10 patients) with typical BOR/BO syndrome, while one patient exhibited only mixed type of hearing loss and inner ear anomalies. One missense and three splice site mutations were identified in EYA1, while no mutations were found in either SIX1 or SIX5 gene; to: PMID: 23840632 - Song et al 2013 - analysed EYA1, SIX1 and SIX5 in 7 families (10 patients) - all with typical BOR/BO syndrome, except for one patient who exhibited only mixed type of hearing loss and inner ear anomalies. One missense and three splice site mutations were identified in EYA1, while no mutations were found in either SIX1 or SIX5 gene
Monogenic hearing loss v2.96 EYA1 Eleanor Williams reviewed gene: EYA1: Rating: ; Mode of pathogenicity: None; Publications: 23840632; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.96 PMP22 Eleanor Williams changed review comment from: Associated with Charcot-Marie-Tooth disease, type 1E #118300 (AD) in which hearing loss is listed as a clinical feature

PMID: 12578939 - Sambuughin et al 2003 - report deafness associated with a demyelinating neuropathy in three individuals of a family in whom a novel 12bp deletion resulting in the deletion of four-amino acid deletion (115-118) in the PMP22 gene was identified. No asymptomatic family members had the deletion nor was it detected in 55 healthy controls.

PMID: 11835375 - Boerkoel et al 2002 - screened PMP22, GJB1, and MPZ contained 159 unrelated patients with primary peripheral demyelinating neuropathy or a primary peripheral axonal neuropathy and report 5 which have heterozygous variants in PMP22, 1 of which had a clinical diagnosis of CMT1 + deafness (variant 82T>C W28R). An affected sibling had the same variant.

PMID: 10330345 - Kovach et al 1999 - analysis of a 7 generation family from central Illinois with autosomal dominant CMT and deafness. In the 31 affected family members, hearing loss ranged from borderline normal to profound hearing loss, with all having at least mild bilateral hearing loss by adulthood. A point mutation was found in affected individuals G->C at position 248 in exon 4 in the heterozygous state (p.Ala67Pro).

PMID: 8355122 - Hamiel et al 1993 - Abstract only accessed. Describe a family with hereditary motor-sensory neuropathy with sensorineural deafness is described; the neurologic features and deafness were apparent in early childhood and infancy.

Summary: 3 cases in which hearing loss is reported in CMT patients with PMP22 variants.; to: Associated with Charcot-Marie-Tooth disease, type 1E #118300 (AD) in which hearing loss is listed as a clinical feature

PMID: 12578939 - Sambuughin et al 2003 - report deafness associated with a demyelinating neuropathy in three individuals of a family in whom a novel 12bp deletion resulting in the deletion of four-amino acid deletion (115-118) in the PMP22 gene was identified (targeted sequencing of PMP22). No asymptomatic family members had the deletion nor was it detected in 55 healthy controls.

PMID: 11835375 - Boerkoel et al 2002 - screened PMP22, GJB1, and MPZ contained 159 unrelated patients with primary peripheral demyelinating neuropathy or a primary peripheral axonal neuropathy and report 5 which have heterozygous variants in PMP22, 1 of which had a clinical diagnosis of CMT1 + deafness (variant 82T>C W28R). An affected sibling had the same variant.

PMID: 10330345 - Kovach et al 1999 - analysis of a 7 generation family from central Illinois with autosomal dominant CMT and deafness. In the 31 affected family members, hearing loss ranged from borderline normal to profound hearing loss, with all having at least mild bilateral hearing loss by adulthood. Following haplotype analysis they sequenced PMP22 and a point mutation was found in affected individuals G->C at position 248 in exon 4 in the heterozygous state (p.Ala67Pro).

PMID: 8355122 - Hamiel et al 1993 - Abstract only accessed. Describe a family with hereditary motor-sensory neuropathy with sensorineural deafness is described; the neurologic features and deafness were apparent in early childhood and infancy.

Summary: 3 cases in which hearing loss is reported in CMT patients with PMP22 variants. In all cases a limited number of genes were sequenced.
Monogenic hearing loss v2.96 PMP22 Eleanor Williams edited their review of gene: PMP22: Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.96 PMP22 Eleanor Williams commented on gene: PMP22
Monogenic hearing loss v2.96 SLC52A3 Arina Puzriakova Classified gene: SLC52A3 as Amber List (moderate evidence)
Monogenic hearing loss v2.96 SLC52A3 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Monogenic hearing loss v2.96 SLC52A3 Arina Puzriakova Gene: slc52a3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.95 SLC52A2 Arina Puzriakova Classified gene: SLC52A2 as Amber List (moderate evidence)
Monogenic hearing loss v2.95 SLC52A2 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Monogenic hearing loss v2.95 SLC52A2 Arina Puzriakova Gene: slc52a2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.94 COL2A1 Eleanor Williams Tag for-review tag was added to gene: COL2A1.
Monogenic hearing loss v2.94 COL2A1 Eleanor Williams changed review comment from: Comment on list classification: Upgrading from red to amber. Should be reviewed by the GMS as to whether it is appropriate to make green.; to: Comment on list classification: Upgrading from red to amber. Should be reviewed by the GMS as to whether it is appropriate to make green. Hearing loss is less predominant in individuals with variants in this gene than in some other Stickler syndrome genes, however if hearing loss is picked up and Stickler syndrome is identified early then eye related symptoms may be treatable.
Monogenic hearing loss v2.94 COL2A1 Eleanor Williams edited their review of gene: COL2A1: Changed rating: GREEN
Monogenic hearing loss v2.94 THOC1 Zornitza Stark gene: THOC1 was added
gene: THOC1 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: THOC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: THOC1 were set to 32776944
Phenotypes for gene: THOC1 were set to Nonsyndromic hearing loss
Review for gene: THOC1 was set to AMBER
Added comment: Missense variant identified and segregated with adult-onset hearing loss in 9 affected family members. 12 unaffected individuals also tested.
Functional studies showed THOC1 was expressed in mouse and zebrafish hair cells. Furthermore, thoc1 deficiency caused the reduction of hair cell numbers in zebrafish and the hypomorphic thoc1 in mouse induced hair cell apoptosis.
Sources: Literature
Monogenic hearing loss v2.94 COCH Zornitza Stark reviewed gene: COCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 16151338, 28116169, 28099493, 9806553, 17561763, 21046548, 26256111, 22931125, 22610276, 18312449, 28733840, 18697796, 29449721, 32939038, 32562050; Phenotypes: Deafness, autosomal dominant 9, MIM# 601369, Deafness, autosomal recessive 110, MIM# 618094; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.94 LMX1A Zornitza Stark edited their review of gene: LMX1A: Added comment: Now 3 families with monoallelic missense variants (2 with dominant inheritance and 1 de novo), and a single biallelic family. Supporting mouse model and in vitro functional assays.; Changed rating: GREEN; Changed publications: 29754270, 29971487, 32840933
Monogenic hearing loss v2.94 COL2A1 Eleanor Williams changed review comment from: Associated with Stickler syndrome, type I #108300 (AD) in OMIM.

PMID: 23110709 - Acke et al 2012 - review the literature to give an overview of hearing loss in Stickler syndrome, correlated with the genotype. 313 patients from 102 families were reviewed. Hearing loss was found in 62.9%, mostly mild to moderate when reported. Mutations in COL11A1 (82.5%) and COL11A2 (94.1%) seem to be more frequently associated with hearing impairment than mutations in COL2A1 (52.2%).

PMID: 27408751 - Kondo et al 2016 - report 21 cases (some familial, most sporadic) with COL2A1 variants. 4/21 showed hearing loss.

PMID: 20179744 - Hoornaert et al 2010 - identified 77 different heterozygous COL2A1 mutations in 100 affected individuals out of a group of 188 individuals referred with a potential diagnosis of Stickler syndrome. 30% of COL2A1-variant positive patients had sensorineural hearing loss. However, over a higher percentage (50%) of patients without a COL2A1 mutation have sensorineural hearing loss.; to: Associated with Stickler syndrome, type I #108300 (AD) in OMIM.

PMID: 23110709 - Acke et al 2012 - review the literature to give an overview of hearing loss in Stickler syndrome, correlated with the genotype. 313 patients from 102 families were reviewed. Hearing loss was found in 62.9%, mostly mild to moderate when reported. Mutations in COL11A1 (82.5%) and COL11A2 (94.1%) seem to be more frequently associated with hearing impairment than mutations in COL2A1 (52.2%).

PMID: 27408751 - Kondo et al 2016 - report 21 cases (some familial, most sporadic) with COL2A1 variants. 4/21 (20%) showed hearing loss.

PMID: 20179744 - Hoornaert et al 2010 - identified 77 different heterozygous COL2A1 mutations in 100 affected individuals out of a group of 188 individuals referred with a potential diagnosis of Stickler syndrome. 30% of COL2A1-variant positive patients had sensorineural hearing loss. However, over a higher percentage (50%) of patients without a COL2A1 mutation have sensorineural hearing loss.
Monogenic hearing loss v2.94 COL11A1 Eleanor Williams Classified gene: COL11A1 as Amber List (moderate evidence)
Monogenic hearing loss v2.94 COL11A1 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team it has been decided that this gene has sufficient cases with hearing loss to be promoted to green. Therefore this gene should be reviewed at the next GMS update.
Monogenic hearing loss v2.94 COL11A1 Eleanor Williams Gene: col11a1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.93 COL11A1 Eleanor Williams edited their review of gene: COL11A1: Changed rating: GREEN
Monogenic hearing loss v2.93 FOXI1 Eleanor Williams Tag for-review tag was added to gene: FOXI1.
Monogenic hearing loss v2.93 FOXI1 Eleanor Williams Classified gene: FOXI1 as Amber List (moderate evidence)
Monogenic hearing loss v2.93 FOXI1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber. There are 2 homozygous and several heterozygous cases reported and it could be promoted to green after GMS review. Although most cases are syndromic hearing loss is a major feature. There is some debate about the whether it is homozygous only or also heterozygously inherited, however the homozygous cases are more convincing.
Monogenic hearing loss v2.93 FOXI1 Eleanor Williams Gene: foxi1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.92 FOXI1 Eleanor Williams edited their review of gene: FOXI1: Changed rating: GREEN
Monogenic hearing loss v2.92 FOXI1 Eleanor Williams reviewed gene: FOXI1: Rating: ; Mode of pathogenicity: None; Publications: 17503324, 29242249, 12642503, 9843211; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.92 FOXF2 Eleanor Williams Classified gene: FOXF2 as Amber List (moderate evidence)
Monogenic hearing loss v2.92 FOXF2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber. 1 case reported with segregation of the variants, plus some mouse model evidence.
Monogenic hearing loss v2.92 FOXF2 Eleanor Williams Gene: foxf2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.91 FOXF2 Eleanor Williams reviewed gene: FOXF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30561639, 22022403; Phenotypes: sensorineural hearing loss (SNHL); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.91 ESRP1 Eleanor Williams Classified gene: ESRP1 as Amber List (moderate evidence)
Monogenic hearing loss v2.91 ESRP1 Eleanor Williams Added comment: Comment on list classification: Changing rating from grey to amber. 1 case with segregation data reported, plus mouse knockout model.
Monogenic hearing loss v2.91 ESRP1 Eleanor Williams Gene: esrp1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.90 ESRP1 Eleanor Williams Phenotypes for gene: ESRP1 were changed from Deafness, autosomal recessive 109, MIM# 618013 to Deafness, autosomal recessive 109, 618013
Monogenic hearing loss v2.89 ESRP1 Eleanor Williams reviewed gene: ESRP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29107558; Phenotypes: ?Deafness, autosomal recessive 109, 618013; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.89 COL11A1 Eleanor Williams Tag for-review tag was added to gene: COL11A1.
Monogenic hearing loss v2.89 COL2A1 Eleanor Williams Classified gene: COL2A1 as Amber List (moderate evidence)
Monogenic hearing loss v2.89 COL2A1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to amber. Should be reviewed by the GMS as to whether it is appropriate to make green.
Monogenic hearing loss v2.89 COL2A1 Eleanor Williams Gene: col2a1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.88 COL2A1 Eleanor Williams Mode of inheritance for gene: COL2A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.87 COL2A1 Eleanor Williams Publications for gene: COL2A1 were set to
Monogenic hearing loss v2.86 COL2A1 Eleanor Williams Phenotypes for gene: COL2A1 were changed from Stickler syndrome, type I, 108300Kniest dysplasia, 156550Achondrogenesis, type II or hypochondrogenesis, 200610SED congenita, 183900SMED Strudwick type, 184250Epiphyseal dysplasia, multiple, with myopia and deafness, 132450Spondyloperipheral dysplasia, 271700SED, Namaqualand typeOsteoarthritis with mild chondrodysplasia, 604864Vitreoretinopathy with phalangeal epiphyseal dysplasiaPlatyspondylic skeletal dysplasia, Torrance type, 151210Otospondylomegaepiphyseal dysplasia, 215150Avascular necrosis of the femoral head, 608805Legg-Calve-Perthes disease, 150600Stickler sydrome, type I, nonsyndromic ocular, 609508Czech dysplasia, 609162; ticklersyndrome,typeI,108300Kniestdysplasia,156550Achondrogenesis,typeIIorhypochondrogenesis,200610SEDcongenita,183900 to Stickler syndrome, type I, 108300
Monogenic hearing loss v2.85 COL9A2 Eleanor Williams Tag for-review tag was added to gene: COL9A2.
Monogenic hearing loss v2.85 COL9A3 Eleanor Williams Tag for-review tag was added to gene: COL9A3.
Monogenic hearing loss v2.85 COL9A3 Eleanor Williams Classified gene: COL9A3 as Amber List (moderate evidence)
Monogenic hearing loss v2.85 COL9A3 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber. 2 cases of a Stickler syndrome phenotype reported, which includes hearing loss.
Monogenic hearing loss v2.85 COL9A3 Eleanor Williams Gene: col9a3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.84 COL9A3 Eleanor Williams Phenotypes for gene: COL9A3 were changed from to Stickler syndrome
Monogenic hearing loss v2.83 COL9A3 Eleanor Williams Publications for gene: COL9A3 were set to
Monogenic hearing loss v2.82 COL9A3 Eleanor Williams Mode of inheritance for gene: COL9A3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.81 COL9A3 Eleanor Williams edited their review of gene: COL9A3: Changed rating: AMBER; Changed publications: 31090205, 24273071; Changed phenotypes: Stickler syndrome; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.81 COL9A3 Eleanor Williams commented on gene: COL9A3
Monogenic hearing loss v2.81 COL9A1 Eleanor Williams changed review comment from: Associated with Stickler syndrome, type IV #614134 in OMIM. No inheritance given.

Summary: 1 Turkish and 2 distantly related Moroccan families with frameshift COL9A1 variants and Stickler syndrome. 2 cases of non-syndromic hearing loss (1 missense, 1 in-frame deletion of several exons).

PMID: 16909383 Van Camp et al 2006 - report a family of Moroccan origin with 4 children affected by Stickler syndrome and 6 unaffected children. The distantly related parents are unaffected. The 4 children showed symptoms characteristic of Stickler syndrome, including moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, and epiphyseal dysplasia. Targeted analysis of COL9A1 resulted in the identification of a homozygous R295X variant in the four affected children. 4 unaffected children and the parents were heterozygous carriers. Two unaffected children did not carry the variant at all.

PMID: 21421862 - Nikopoulos et al 2011 - Report two consanguineous families with children with Stickler syndrome. One Turkish family has two affected sisters, the other Moroccan family has one affected boy. The Turkish girls were found to have a homozygous COL9A1 mutation (p.R507X) while the Moroccan boy had the same variant found in the Moroccan family published by Van Camp et al 2006 (p.R295X). Phenotypic features include myopia, cataracts, distinct vitreous changes, progressive chorioretinal degeneration, and exudative and rhegmatogenous retinal detachments. All three had sensorineural hearing loss and epiphyseal dysplasia. Haplotype analysis of the Moroccan family showed they shared the identical disease haplotype in the 2-cM area encompassing COL9A1 as the previously described Moroccan family, indicating a possible relationship.

PMID: 23967202 - Miyagawa et al 2013 - report one case of a missense variant (NM_001851.3, c.2395G>C, p.G799R)in COL9A1 in a patient with sporadic early onset hearing loss, identified by targeted exome sequencing. Detailed phenotype information not available.

PMID: 31315069 - Hofrichter et al 2019 - report 2 patients with non-syndromic HL from an Iranian family. Both siblings were homozygous for a 44.6 kb in-frame deletion spanning exons 6 to 33 of COL9A1. The parents were heterozygous for the deletion. The initially presented non-syndromic HL at the age of 28 years, but clinical follow up has not been undertaken.; to: Associated with Stickler syndrome, type IV #614134 in OMIM. No inheritance given.

Summary: 1 Turkish and 1 unknown ethnicity family with R507X variants and 2 distantly related Moroccan families with R295X COL9A1 variants and Stickler syndrome. 2 cases of non-syndromic hearing loss (1 missense, 1 in-frame deletion of several exons).

PMID: 16909383 Van Camp et al 2006 - report a family of Moroccan origin with 4 children affected by Stickler syndrome and 6 unaffected children. The distantly related parents are unaffected. The 4 children showed symptoms characteristic of Stickler syndrome, including moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, and epiphyseal dysplasia. Targeted analysis of COL9A1 resulted in the identification of a homozygous R295X variant in the four affected children. 4 unaffected children and the parents were heterozygous carriers. Two unaffected children did not carry the variant at all.

PMID: 21421862 - Nikopoulos et al 2011 - Report two consanguineous families with children with Stickler syndrome. One Turkish family has two affected sisters, the other Moroccan family has one affected boy. The Turkish girls were found to have a homozygous COL9A1 mutation (p.R507X) while the Moroccan boy had the same variant found in the Moroccan family published by Van Camp et al 2006 (p.R295X). Phenotypic features include myopia, cataracts, distinct vitreous changes, progressive chorioretinal degeneration, and exudative and rhegmatogenous retinal detachments. All three had sensorineural hearing loss and epiphyseal dysplasia. Haplotype analysis of the Moroccan family showed they shared the identical disease haplotype in the 2-cM area encompassing COL9A1 as the previously described Moroccan family, indicating a possible relationship.

PMID: 23967202 - Miyagawa et al 2013 - report one case of a missense variant (NM_001851.3, c.2395G>C, p.G799R)in COL9A1 in a patient with sporadic early onset hearing loss, identified by targeted exome sequencing. Detailed phenotype information not available.

PMID: 31315069 - Hofrichter et al 2019 - report 2 patients with non-syndromic HL from an Iranian family. Both siblings were homozygous for a 44.6 kb in-frame deletion spanning exons 6 to 33 of COL9A1. The parents were heterozygous for the deletion. The initially presented non-syndromic HL at the age of 28 years, but clinical follow up has not been undertaken.

PMID: 31090205 - Nixon et al 2019 - report 1 case of a 6 year old child with a homozygous nonsense variant in COL9A1 (c.1519C>T, p.(Arg507Ter)) and a diagnosis of Stickler syndrome. This variant has been described previously (Nikopoulos et al., 2011). The child had high‐frequency sensorineural hearing loss.
Monogenic hearing loss v2.81 COL9A2 Eleanor Williams Phenotypes for gene: COL9A2 were changed from Epiphyseal dysplasia, multiple, 2, 600204{Intervertebral disc disease, susceptibility to}, 603932Stickler syndrome, type V, 614284; Epiphysealdysplasia,multiple,2,600204{Intervertebraldiscdisease,susceptibilityto},603932Sticklersyndrome,typeV,614284 to ?Stickler syndrome, type V, 614284
Monogenic hearing loss v2.80 COL9A2 Eleanor Williams Publications for gene: COL9A2 were set to
Monogenic hearing loss v2.79 COL9A2 Eleanor Williams Added comment: Comment on mode of inheritance: 3 reported cases are all homozygous
Monogenic hearing loss v2.79 COL9A2 Eleanor Williams Mode of inheritance for gene: COL9A2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.78 COL9A2 Eleanor Williams Classified gene: COL9A2 as Amber List (moderate evidence)
Monogenic hearing loss v2.78 COL9A2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber, but sufficient cases to rate green following GMS review of appropriateness of this gene for a non-syndromic hearing loss panel.
Monogenic hearing loss v2.78 COL9A2 Eleanor Williams Gene: col9a2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.77 COL9A2 Eleanor Williams reviewed gene: COL9A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21671392, 31090205; Phenotypes: ?Stickler syndrome, type V, 614284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.77 COL11A1 Eleanor Williams commented on gene: COL11A1: PMID: 23967202 - Miyagawa et al 2013 - report 3 missense variants in Japanese hearing loss patients through targeted exome sequencing. 1 familial case shown with two affected siblings. They suggest the inheritance is autosomal dominant.
Monogenic hearing loss v2.77 COL9A1 Eleanor Williams Tag for-review tag was added to gene: COL9A1.
Monogenic hearing loss v2.77 COL9A1 Eleanor Williams Classified gene: COL9A1 as Amber List (moderate evidence)
Monogenic hearing loss v2.77 COL9A1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to amber, but maybe appropriate for green rating following GMS review.
Monogenic hearing loss v2.77 COL9A1 Eleanor Williams Gene: col9a1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.76 COL9A1 Eleanor Williams Phenotypes for gene: COL9A1 were changed from Epiphyseal dysplasia, multiple, 6, 614135Stickler syndrome, type IV, 614134; Epiphysealdysplasia,multiple,6,614135Sticklersyndrome,typeIV,614134 to Stickler syndrome, type IV, 614134; hearing loss
Monogenic hearing loss v2.75 COL9A1 Eleanor Williams Publications for gene: COL9A1 were set to
Monogenic hearing loss v2.74 COL9A1 Eleanor Williams changed review comment from: Associated with Stickler syndrome, type IV #614134 in OMIM. No inheritance given.

Summary: 1 Turkish and 2 distantly related Moroccan families with frameshift COL9A1 variants and Stickler syndrome. 2 cases on non-syndromic hearing loss (1 missense, 1 in-frame deletion of several exons).

PMID: 16909383 Van Camp et al 2006 - report a family of Moroccan origin with 4 children affected by Stickler syndrome and 6 unaffected children. The distantly related parents are unaffected. The 4 children showed symptoms characteristic of Stickler syndrome, including moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, and epiphyseal dysplasia. Targeted analysis of COL9A1 resulted in the identification of a homozygous R295X variant in the four affected children. 4 unaffected children and the parents were heterozygous carriers. Two unaffected children did not carry the variant at all.

PMID: 21421862 - Nikopoulos et al 2011 - Report two consanguineous families with children with Stickler syndrome. One Turkish family has two affected sisters, the other Moroccan family has one affected boy. The Turkish girls were found to have a homozygous COL9A1 mutation (p.R507X) while the Moroccan boy had the same variant found in the Moroccan family published by Van Camp et al 2006 (p.R295X). Phenotypic features include myopia, cataracts, distinct vitreous changes, progressive chorioretinal degeneration, and exudative and rhegmatogenous retinal detachments. All three had sensorineural hearing loss and epiphyseal dysplasia. Haplotype analysis of the Moroccan family showed they shared the identical disease haplotype in the 2-cM area encompassing COL9A1 as the previously described Moroccan family, indicating a possible relationship.

PMID: 23967202 - Miyagawa et al 2013 - report one case of a missense variant (NM_001851.3, c.2395G>C, p.G799R)in COL9A1 in a patient with sporadic early onset hearing loss, identified by targeted exome sequencing. Detailed phenotype information not available.

PMID: 31315069 - Hofrichter et al 2019 - report 2 patients with non-syndromic HL from an Iranian family. Both siblings were homozygous for a 44.6 kb in-frame deletion spanning exons 6 to 33 of COL9A1. The parents were heterozygous for the deletion. The initially presented non-syndromic HL at the age of 28 years, but clinical follow up has not been undertaken.; to: Associated with Stickler syndrome, type IV #614134 in OMIM. No inheritance given.

Summary: 1 Turkish and 2 distantly related Moroccan families with frameshift COL9A1 variants and Stickler syndrome. 2 cases of non-syndromic hearing loss (1 missense, 1 in-frame deletion of several exons).

PMID: 16909383 Van Camp et al 2006 - report a family of Moroccan origin with 4 children affected by Stickler syndrome and 6 unaffected children. The distantly related parents are unaffected. The 4 children showed symptoms characteristic of Stickler syndrome, including moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, and epiphyseal dysplasia. Targeted analysis of COL9A1 resulted in the identification of a homozygous R295X variant in the four affected children. 4 unaffected children and the parents were heterozygous carriers. Two unaffected children did not carry the variant at all.

PMID: 21421862 - Nikopoulos et al 2011 - Report two consanguineous families with children with Stickler syndrome. One Turkish family has two affected sisters, the other Moroccan family has one affected boy. The Turkish girls were found to have a homozygous COL9A1 mutation (p.R507X) while the Moroccan boy had the same variant found in the Moroccan family published by Van Camp et al 2006 (p.R295X). Phenotypic features include myopia, cataracts, distinct vitreous changes, progressive chorioretinal degeneration, and exudative and rhegmatogenous retinal detachments. All three had sensorineural hearing loss and epiphyseal dysplasia. Haplotype analysis of the Moroccan family showed they shared the identical disease haplotype in the 2-cM area encompassing COL9A1 as the previously described Moroccan family, indicating a possible relationship.

PMID: 23967202 - Miyagawa et al 2013 - report one case of a missense variant (NM_001851.3, c.2395G>C, p.G799R)in COL9A1 in a patient with sporadic early onset hearing loss, identified by targeted exome sequencing. Detailed phenotype information not available.

PMID: 31315069 - Hofrichter et al 2019 - report 2 patients with non-syndromic HL from an Iranian family. Both siblings were homozygous for a 44.6 kb in-frame deletion spanning exons 6 to 33 of COL9A1. The parents were heterozygous for the deletion. The initially presented non-syndromic HL at the age of 28 years, but clinical follow up has not been undertaken.
Monogenic hearing loss v2.74 COL9A1 Eleanor Williams reviewed gene: COL9A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16909383, 21421862, 23967202, 31315069; Phenotypes: Stickler syndrome, type IV, 614134, hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.74 COL2A1 Eleanor Williams edited their review of gene: COL2A1: Changed rating: AMBER; Changed publications: 23110709, 27408751, 20179744; Changed phenotypes: Stickler syndrome, type I, 108300; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.74 COL2A1 Eleanor Williams commented on gene: COL2A1
Monogenic hearing loss v2.74 COL11A1 Eleanor Williams Phenotypes for gene: COL11A1 were changed from Stickler syndrome, type II, 604841Marshall syndrome, 154780{Lumbar disc herniation, susceptibility to}, 603932Fibrochondrogenesis, 228520; Sticklersyndrome,typeII,604841 to Stickler syndrome, type II, MIM#604841; Deafness, autosomal dominant 37, MIM#618533
Monogenic hearing loss v2.73 COL11A1 Eleanor Williams Publications for gene: COL11A1 were set to
Monogenic hearing loss v2.72 COL11A1 Eleanor Williams Mode of inheritance for gene: COL11A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.71 COL11A1 Eleanor Williams Classified gene: COL11A1 as Amber List (moderate evidence)
Monogenic hearing loss v2.71 COL11A1 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. 1 case of non-syndromic hearing loss in a large pedigree. Other reports are from patients with Stickler/Marshal syndrome.
Monogenic hearing loss v2.71 COL11A1 Eleanor Williams Gene: col11a1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.70 COL11A1 Eleanor Williams reviewed gene: COL11A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30245514, 17236192; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.70 ATP6V1B2 Eleanor Williams Phenotypes for gene: ATP6V1B2 were changed from to Deafness, congenital, with onychodystrophy, autosomal dominant, 124480; Zimmermann-Laband syndrome 2, 616455
Monogenic hearing loss v2.69 ATP6V1B2 Eleanor Williams Publications for gene: ATP6V1B2 were set to
Monogenic hearing loss v2.68 ATP6V1B2 Eleanor Williams Tag for-review tag was added to gene: ATP6V1B2.
Monogenic hearing loss v2.68 ATP6V1B2 Eleanor Williams changed review comment from: Comment on list classification: The rating of this gene should be reviewed after consultation with the Genomics England clinical team and at the next GMS review.; to: Comment on list classification: Sufficient cases with Deafness, congenital, with onychodystrophy to rate green. This gene should be reviewed at the next GMS update.
Monogenic hearing loss v2.68 ATP6V1B2 Eleanor Williams changed review comment from: Adding gene at request of Alistair Pagnamenta (University of Oxford).

PMID: 32873933 Beauregard-Lacroix et al 2020 - identified the same truncating variant in ATP6V1B2 (NM_001693.4:c.1516C>T; p.Arg506*) in nine individuals from eight unrelated families with DOORS syndrome. All individuals presented with deafness as well as as onychodystrophy and abnormal fingers and/or toes. In addition, all families but one had developmental delay or intellectual disability and five individuals had epilepsy. Two additional familes with dominant deafness onychodystrophy (DDOD) syndrome also had the same variant in ATP6V1B2. Abstract only accessed.
Sources: Expert Review, Literature; to: Adding gene at request of Alistair Pagnamenta (University of Oxford).

Associated with Deafness, congenital, with onychodystrophy, autosomal dominant #124480 (AD) and Zimmermann-Laband syndrome 2 #616455 (AD) in OMIM.

PMID: 32873933 Beauregard-Lacroix et al 2020 - identified the same truncating variant in ATP6V1B2 (NM_001693.4:c.1516C>T; p.Arg506*) in nine individuals from eight unrelated families with DOORS syndrome. All individuals presented with deafness as well as as onychodystrophy and abnormal fingers and/or toes. In addition, all families but one had developmental delay or intellectual disability and five individuals had epilepsy. Two additional familes with dominant deafness onychodystrophy (DDOD) syndrome also had the same variant in ATP6V1B2. Abstract only accessed.

PMID: 28396750 Menendez et al 2017 - report a Guatemalan famliy with one child with deafness–onychodystrophy. The proband was found to be heterozygous for c.1516C>T [p.(Arg506*)] in ATP6V1B2. Neither parents or sisters had this variant.

PMID: 24913193 Yuan et al 2014 - report 3 Chinese families with severe congenital sensorineural hearing loss, absence of nails and aplasia of the middle phalanx in the fifth fingers, but no inner ear malformation or intellectual disability. Using exome sequencing an identical heterozygous de novo c.1516 C>T (p.Arg506X) mutation in ATP6V1B2 was verified in two probands. In the third family the same variant was found by Sanger sequencing. A cochlea-specific Atp6v1b2-knockdown mouse model demonstrates that Atp6v1b2 deficiency leads to severe sensorineural hearing loss.
Monogenic hearing loss v2.68 ATP6V1B2 Eleanor Williams Classified gene: ATP6V1B2 as Amber List (moderate evidence)
Monogenic hearing loss v2.68 ATP6V1B2 Eleanor Williams Gene: atp6v1b2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.67 ATP6V1B2 Eleanor Williams Classified gene: ATP6V1B2 as Red List (low evidence)
Monogenic hearing loss v2.67 ATP6V1B2 Eleanor Williams Added comment: Comment on list classification: The rating of this gene should be reviewed after consultation with the Genomics England clinical team and at the next GMS review.
Monogenic hearing loss v2.67 ATP6V1B2 Eleanor Williams Gene: atp6v1b2 has been classified as Red List (Low Evidence).
Monogenic hearing loss v2.66 ATP6V1B2 Eleanor Williams edited their review of gene: ATP6V1B2: Changed rating: GREEN
Monogenic hearing loss v2.66 ATP6V1B2 Eleanor Williams gene: ATP6V1B2 was added
gene: ATP6V1B2 was added to Hearing loss. Sources: Expert Review,Literature
Mode of inheritance for gene: ATP6V1B2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added comment: Adding gene at request of Alistair Pagnamenta (University of Oxford).

PMID: 32873933 Beauregard-Lacroix et al 2020 - identified the same truncating variant in ATP6V1B2 (NM_001693.4:c.1516C>T; p.Arg506*) in nine individuals from eight unrelated families with DOORS syndrome. All individuals presented with deafness as well as as onychodystrophy and abnormal fingers and/or toes. In addition, all families but one had developmental delay or intellectual disability and five individuals had epilepsy. Two additional familes with dominant deafness onychodystrophy (DDOD) syndrome also had the same variant in ATP6V1B2. Abstract only accessed.
Sources: Expert Review, Literature
Monogenic hearing loss v2.65 SOX2 Eleanor Williams Tag for-review tag was added to gene: SOX2.
Monogenic hearing loss v2.65 SOX2 Eleanor Williams Classified gene: SOX2 as Green List (high evidence)
Monogenic hearing loss v2.65 SOX2 Eleanor Williams Added comment: Comment on list classification: Limited evidence for green rating. Should be reviewed at the next major review of this panel.
Monogenic hearing loss v2.65 SOX2 Eleanor Williams Gene: sox2 has been classified as Green List (High Evidence).
Monogenic hearing loss v2.64 SOX2 Eleanor Williams Publications for gene: SOX2 were set to PMID:10564870; 11135495; 12002146; 12036291; 12461687; 12612584; 14517545; 15240551; 15346919; 15389708; 15812812; 15846349; 16145681; 16283891; 16470798; 16543359; 16651659; 16712695; 16892407; 16904174; 16932809; 17015430; 17219395; 17515932; 17522155; 17554336; 17554338; 18029452; 18157115; 18285410; 18385377; 18806776; 18818365; 18831064; 18845712; 19254784; 19403656; 19801978; 19898493; 19921648; 20803647; 21326281; 21331042; 21532573; 21919124; 24048479; 24909994; 7849401; 8741917
Monogenic hearing loss v2.63 SOX2 Eleanor Williams edited their review of gene: SOX2: Changed rating: AMBER
Monogenic hearing loss v2.63 SOX2 Eleanor Williams commented on gene: SOX2
Monogenic hearing loss v2.63 TOP2B Zornitza Stark edited their review of gene: TOP2B: Changed rating: AMBER
Monogenic hearing loss v2.63 SPATC1L Zornitza Stark edited their review of gene: SPATC1L: Changed rating: AMBER
Monogenic hearing loss v2.63 SPATC1L Eleanor Williams Classified gene: SPATC1L as Amber List (moderate evidence)
Monogenic hearing loss v2.63 SPATC1L Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. 3 cases reported but only one with segregation data.
Monogenic hearing loss v2.63 SPATC1L Eleanor Williams Gene: spatc1l has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.62 SPATC1L Eleanor Williams Added comment: Comment on mode of inheritance: I am not sure from the publication about the mode of inheritance. I read it that each family had one variant (no compound hets) and therefore the mode of inheritance would be mono-allelic. However, leaving as both monallelic and biallelic for now due to expert review.
Monogenic hearing loss v2.62 SPATC1L Eleanor Williams Mode of inheritance for gene: SPATC1L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.61 SPATC1L Eleanor Williams reviewed gene: SPATC1L: Rating: AMBER; Mode of pathogenicity: None; Publications: 30177775; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v2.61 SPNS2 Eleanor Williams Classified gene: SPNS2 as Amber List (moderate evidence)
Monogenic hearing loss v2.61 SPNS2 Eleanor Williams Added comment: Comment on list classification: Updating the rating from grey to amber. 1 reported case plus mouse model.
Monogenic hearing loss v2.61 SPNS2 Eleanor Williams Gene: spns2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.60 SPNS2 Eleanor Williams reviewed gene: SPNS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30973865, 25356849; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.60 TMTC2 Eleanor Williams Classified gene: TMTC2 as Amber List (moderate evidence)
Monogenic hearing loss v2.60 TMTC2 Eleanor Williams Added comment: Comment on list classification: Changing rating from grey to amber. Two families reported. Same variant in each. Both northern european decent.
Monogenic hearing loss v2.60 TMTC2 Eleanor Williams Gene: tmtc2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.59 TMTC2 Eleanor Williams Phenotypes for gene: TMTC2 were changed from Deafness to Deafness; Sensorineural hearing loss
Monogenic hearing loss v2.58 TMTC2 Eleanor Williams Added comment: Comment on mode of inheritance: Changing to imprinted status unknown. In one family the trait had been passed through the maternal side for two generations, but more evidence needed before saying paternally imprinted.
Monogenic hearing loss v2.58 TMTC2 Eleanor Williams Mode of inheritance for gene: TMTC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.57 TMTC2 Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM.

PMID: 29671961- Guillen‐Ahlers et al 2018 - report a mother and son with of Northern European descent (mother and son) with Sensorineural hearing loss were found by exome sequencing to share a variant (rs35725509, missense variant) in the TMTC2 gene. This variant showed a minor allele frequency below 1% in 2,203 individuals of European American (EA) ancestry (NHLBI GO Exome Sequencing Project.


PMID: 27311106 - Runge et al 2016 - report a large multigenerational Northern European family in which 9 family members had bilateral, symmetric, progressive Sensorineural hearing loss that reached severe to profound loss in childhood. Using exome sequencing and linkage and association analyses they identified a fully penetrant sequence variant (rs35725509) in the TMTC2 gene region. The variant segregates with SNHL in the family. However, the mutation is found in a relatively high percentage of individuals of Northern European descent in the 1000 Genomes and Exome Sequencing (http://evs.gs.washington.edu/EVS/) European call sets (1% and 0.8%, respectively).; to: Not associated with a phenotype in OMIM.

PMID: 29671961- Guillen‐Ahlers et al 2018 - report a mother and son with of Northern European descent (mother and son) with Sensorineural hearing loss were found by exome sequencing to share a variant (rs35725509, missense variant) in the TMTC2 gene. This variant showed a minor allele frequency below 1% in 2,203 individuals of European American (EA) ancestry (NHLBI GO Exome Sequencing Project. In two generations, the trait has been passed through the maternal side


PMID: 27311106 - Runge et al 2016 - report a large multigenerational Northern European family in which 9 family members had bilateral, symmetric, progressive Sensorineural hearing loss that reached severe to profound loss in childhood. Using exome sequencing and linkage and association analyses they identified a fully penetrant sequence variant (rs35725509) in the TMTC2 gene region. The variant segregates with SNHL in the family. However, the mutation is found in a relatively high percentage of individuals of Northern European descent in the 1000 Genomes and Exome Sequencing (http://evs.gs.washington.edu/EVS/) European call sets (1% and 0.8%, respectively).
Monogenic hearing loss v2.57 TMTC2 Eleanor Williams edited their review of gene: TMTC2: Changed rating: AMBER; Changed publications: 29671961, 27311106; Changed phenotypes: Sensorineural hearing loss; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.57 TMTC2 Eleanor Williams commented on gene: TMTC2
Monogenic hearing loss v2.57 TOP2B Eleanor Williams Phenotypes for gene: TOP2B were changed from Deafness, autosomal dominant to Deafness, autosomal dominant; nonsyndromic hearing loss
Monogenic hearing loss v2.56 TOP2B Eleanor Williams Classified gene: TOP2B as Amber List (moderate evidence)
Monogenic hearing loss v2.56 TOP2B Eleanor Williams Added comment: Comment on list classification: Changing the rating from grey to amber. 1 familial case plus 3 sporadic cases reported. Supportive animal model. All reported in one publication so will wait until there is an additional supporting familial case before rating green.
Monogenic hearing loss v2.56 TOP2B Eleanor Williams Gene: top2b has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.55 TOP2B Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM.

PMID: 31198993 - Xia et al 2019 - Whole-exome sequencing was performed on seven affected and six unaffected members in a large Chinese family with autosomal-dominant nonsyndromic hearing loss. A variant in TOP2B (c.G4837C:p.D1613H) segregated with hearing loss in this family. Two variants other of TOP2B were detected in 66 sporadic patients with hearing loss. In zebrafish, top2b knockdown led to defects in the inner ears and caused downregulation of akt which resulted in inactivation of PI3K-Akt signalling.; to: Not associated with a phenotype in OMIM.

PMID: 31198993 - Xia et al 2019 - Whole-exome sequencing was performed on seven affected and six unaffected members in a large Chinese family with autosomal-dominant nonsyndromic hearing loss. A variant in TOP2B (c.G4837C:p.D1613H) segregated with hearing loss in this family. Two other variants of TOP2B were detected in 66 sporadic patients with hearing loss (p.L721F and p. K1435del, plus another case with p.D1613H). In zebrafish, top2b knockdown led to defects in the inner ears and caused downregulation of akt which resulted in inactivation of PI3K-Akt signalling.
Monogenic hearing loss v2.55 TOP2B Eleanor Williams reviewed gene: TOP2B: Rating: AMBER; Mode of pathogenicity: None; Publications: 31198993; Phenotypes: nonsyndromic hearing loss; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.55 WBP2 Eleanor Williams Phenotypes for gene: WBP2 were changed from Deafness, autosomal recessive 107, MIM#617639 to Deafness, autosomal recessive 107, 617639
Monogenic hearing loss v2.54 WBP2 Eleanor Williams Classified gene: WBP2 as Amber List (moderate evidence)
Monogenic hearing loss v2.54 WBP2 Eleanor Williams Added comment: Comment on list classification: Changing the rating from grey to Amber. 2 cases plus mouse model but all from one paper. No further evidence since 2016.
Monogenic hearing loss v2.54 WBP2 Eleanor Williams Gene: wbp2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.53 WBP2 Eleanor Williams edited their review of gene: WBP2: Changed rating: AMBER; Changed publications: 26881968; Changed phenotypes: Deafness, autosomal recessive 107 617639; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.53 WBP2 Eleanor Williams commented on gene: WBP2
Monogenic hearing loss v2.53 FDXR Eleanor Williams edited their review of gene: FDXR: Changed rating: GREEN
Monogenic hearing loss v2.53 FDXR Eleanor Williams Tag for-review tag was added to gene: FDXR.
Monogenic hearing loss v2.53 FDXR Eleanor Williams changed review comment from: Comment on list classification: There are 3 cases where hearing loss is reported as the first symptom, although there are other cases in which variants in this gene do not result in hearing loss, or hearing loss after an optic phenotype.; to: Comment on list classification: There are 3 cases where hearing loss is reported as the first symptom, although there are other cases in which variants in this gene do not result in hearing loss, or hearing loss after an optic phenotype. Rating amber for now until this gene can be reviewed by the GMS.
Monogenic hearing loss v2.53 FDXR Eleanor Williams Classified gene: FDXR as Amber List (moderate evidence)
Monogenic hearing loss v2.53 FDXR Eleanor Williams Added comment: Comment on list classification: There are 3 cases where hearing loss is reported as the first symptom, although there are other cases in which variants in this gene do not result in hearing loss, or hearing loss after an optic phenotype.
Monogenic hearing loss v2.53 FDXR Eleanor Williams Gene: fdxr has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.52 FDXR Eleanor Williams changed review comment from: Associated with Auditory neuropathy and optic atrophy #617717 (AR) in OMIM.

PMID: 28965846 - Paul et al 2017 - report 8 individuals from 4 families from Tunisia, Algeria, France and Russia/Azerbaijan. All were affected by auditory neuropathy and optic atrophy with first onset before age 20. In 4/8 individuals hearing loss was the first symptom. In all cases biallelic (homozygous or compound het) variants in FDXR were found (exome sequencing in family 1, direct sequencing in the other 3 families). The variants segregated with the phenotype in family 1 (homozygous variant). Parental DNA was not available for other families. No FDXR variants were found in 86 other patients with different types of hearing loss. FDXR encodes a mitochondrial NADPH. FDXR levels were decreased in fibroblasts derived from patients in two of the families. Functional studies suggest a defect in iron homeostasis. Yeast studies showed that some of the FDXR variants failed to rescue growth defects in FDXR ortholog arh1 knockouts, but wildtype FDXR was able to rescue the defect.

PMID: 29040572 (Peng et al 2017) - report 17 individuals from 13 unrelated families with recessive mutations in FDXR. The core clinical features were optic atrophy, ataxia, and hypotonia but hearing loss was also noted as a less common phenotype.

Note, other cases reported with variants FDXR but no hearing loss phenotype e.g. PMID: 30250212 (Slone et al, 2018) ; to: Associated with Auditory neuropathy and optic atrophy #617717 (AR) in OMIM.

PMID: 28965846 - Paul et al 2017 - report 8 individuals from 4 families from Tunisia, Algeria, France and Russia/Azerbaijan. All were affected by auditory neuropathy and optic atrophy with first onset before age 20. In 4/8 individuals from 3 families hearing loss was the first symptom. In all cases biallelic (homozygous or compound het) variants in FDXR were found (exome sequencing in family 1, direct sequencing in the other 3 families). The variants segregated with the phenotype in family 1 (homozygous variant). Parental DNA was not available for other families. No FDXR variants were found in 86 other patients with different types of hearing loss. FDXR encodes a mitochondrial NADPH. FDXR levels were decreased in fibroblasts derived from patients in two of the families. Functional studies suggest a defect in iron homeostasis. Yeast studies showed that some of the FDXR variants failed to rescue growth defects in FDXR ortholog arh1 knockouts, but wildtype FDXR was able to rescue the defect.

PMID: 29040572 (Peng et al 2017) - report 17 individuals from 13 unrelated families with recessive mutations in FDXR. The core clinical features were optic atrophy, ataxia, and hypotonia but hearing loss was also noted as a less common phenotype.

Note, other cases reported with variants FDXR but no hearing loss phenotype e.g. PMID: 30250212 (Slone et al, 2018)
Monogenic hearing loss v2.52 FDXR Eleanor Williams changed review comment from: Associated with Auditory neuropathy and optic atrophy #617717 (AR) in OMIM.

PMID: 28965846 - Paul et al 2017 - report 8 individuals from 4 families from Tunisia, Algeria, France and Russia/Azerbaijan. All were affected by auditory neuropathy and optic atrophy with first onset before age 20. In 4/8 individuals hearing loss was the first symptom. In all cases biallelic (homozygous or compound het) variants in FDXR were found (exome sequencing in family 1, direct sequencing in the other 3 families). The variants segregated with the phenotype in family 1 (homozygous variant). Parental DNA was not available for other families. No FDXR variants were found in 86 other patients with different types of hearing loss. FDXR encodes a mitochondrial NADPH. FDXR levels were decreased in fibroblasts derived from patients in two of the families. Functional studies suggest a defect in iron homeostasis. Yeast studies showed that some of the FDXR variants failed to rescue growth defects in FDXR ortholog arh1 knockouts, but wildtype FDXR was able to rescue the defect.; to: Associated with Auditory neuropathy and optic atrophy #617717 (AR) in OMIM.

PMID: 28965846 - Paul et al 2017 - report 8 individuals from 4 families from Tunisia, Algeria, France and Russia/Azerbaijan. All were affected by auditory neuropathy and optic atrophy with first onset before age 20. In 4/8 individuals hearing loss was the first symptom. In all cases biallelic (homozygous or compound het) variants in FDXR were found (exome sequencing in family 1, direct sequencing in the other 3 families). The variants segregated with the phenotype in family 1 (homozygous variant). Parental DNA was not available for other families. No FDXR variants were found in 86 other patients with different types of hearing loss. FDXR encodes a mitochondrial NADPH. FDXR levels were decreased in fibroblasts derived from patients in two of the families. Functional studies suggest a defect in iron homeostasis. Yeast studies showed that some of the FDXR variants failed to rescue growth defects in FDXR ortholog arh1 knockouts, but wildtype FDXR was able to rescue the defect.

PMID: 29040572 (Peng et al 2017) - report 17 individuals from 13 unrelated families with recessive mutations in FDXR. The core clinical features were optic atrophy, ataxia, and hypotonia but hearing loss was also noted as a less common phenotype.

Note, other cases reported with variants FDXR but no hearing loss phenotype e.g. PMID: 30250212 (Slone et al, 2018)
Monogenic hearing loss v2.52 FDXR Eleanor Williams reviewed gene: FDXR: Rating: ; Mode of pathogenicity: None; Publications: 28965846; Phenotypes: Auditory neuropathy and optic atrophy 617717; Mode of inheritance: None
Monogenic hearing loss v2.52 CISD2 Eleanor Williams Tag for-review tag was added to gene: CISD2.
Monogenic hearing loss v2.52 CISD2 Eleanor Williams Classified gene: CISD2 as Amber List (moderate evidence)
Monogenic hearing loss v2.52 CISD2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber as several cases reported with hearing loss as a feature, but not as the first presenting feature.
Monogenic hearing loss v2.52 CISD2 Eleanor Williams Gene: cisd2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.51 CISD2 Eleanor Williams Phenotypes for gene: CISD2 were changed from hearing loss to hearing loss; Wolfram syndrome 2 604928
Monogenic hearing loss v2.50 CISD2 Eleanor Williams Publications for gene: CISD2 were set to
Monogenic hearing loss v2.49 CISD2 Eleanor Williams edited their review of gene: CISD2: Changed rating: AMBER; Changed publications: 10739754, 17846994, 25056293, 25371195; Changed phenotypes: Wolfram syndrome 2 #604928; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.49 CISD2 Eleanor Williams commented on gene: CISD2
Monogenic hearing loss v2.49 SLC12A2 Arina Puzriakova Phenotypes for gene: SLC12A2 were changed from to Bilateral sensorineural hearing loss; Intellectual disability; Secretory defects
Monogenic hearing loss v2.48 SLC12A2 Arina Puzriakova Publications for gene: SLC12A2 were set to
Monogenic hearing loss v2.47 SLC12A2 Arina Puzriakova Mode of inheritance for gene: SLC12A2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.46 SLC12A2 Arina Puzriakova Classified gene: SLC12A2 as Amber List (moderate evidence)
Monogenic hearing loss v2.46 SLC12A2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review - at least 10 unrelated cases (and animal models) presenting significant sensorineural hearing loss, associated with variants in SLC12A2.
Monogenic hearing loss v2.46 SLC12A2 Arina Puzriakova Gene: slc12a2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.45 SLC12A2 Arina Puzriakova Tag for-review tag was added to gene: SLC12A2.
Monogenic hearing loss v2.45 SLC12A2 Arina Puzriakova reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30740830, 32294086, 32754646, 32658972; Phenotypes: Bilateral sensorineural hearing loss, Intellectual disability, Secretory defects; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.45 TIMM8A Arina Puzriakova reviewed gene: TIMM8A: Rating: ; Mode of pathogenicity: None; Publications: 32820032; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Monogenic hearing loss v2.45 DNMT1 Eleanor Williams Publications for gene: DNMT1 were set to PMID:10325416; 10433969; 10449766; 10545955; 10615135; 10721735; 10753866; 10801130; 10888872; 10888886; 11005794; 11074872; 11290321; 11728338; 11884600; 11932749; 11940649; 12145218; 12473678; 12496760; 12702876; 12915469; 14615517; 14684836; 14749379; 14978102; 15215866; 15311210; 1559980; 15657147; 15684088; 15870198; 1594447; 1606615; 16357870; 16998846; 17312023; 17322882; 17359920; 17470536; 17673620; 17960246; 17994007; 18194272; 19098913; 19246518; 19433415; 1968655; 20081831; 2014266; 21163962; 21532572; 22323818; 22328086; 23365052; 24013172; 24107992; 3210246; 7898717; 8747854; 8917520; 8940105; 9302295; 9333948; 9449671
Monogenic hearing loss v2.44 DNMT1 Eleanor Williams reviewed gene: DNMT1: Rating: ; Mode of pathogenicity: None; Publications: 31984424; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v2.44 RIPOR2 Arina Puzriakova Added comment: Comment on mode of inheritance: Only two publications, describing different patterns of inheritance (AR or AD).
Monogenic hearing loss v2.44 RIPOR2 Arina Puzriakova Mode of inheritance for gene: RIPOR2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.43 RIPOR2 Arina Puzriakova Classified gene: RIPOR2 as Amber List (moderate evidence)
Monogenic hearing loss v2.43 RIPOR2 Arina Puzriakova Added comment: Comment on list classification: Recent publication described several families, but with a founder variant. Therefore currently still insufficient cases for a rating upgrade.
Monogenic hearing loss v2.43 RIPOR2 Arina Puzriakova Gene: ripor2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.42 RIPOR2 Arina Puzriakova reviewed gene: RIPOR2: Rating: ; Mode of pathogenicity: None; Publications: 32631815; Phenotypes: Sensorineural hearing loss; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v2.42 MN1 Arina Puzriakova Classified gene: MN1 as Amber List (moderate evidence)
Monogenic hearing loss v2.42 MN1 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - added to this panel following suggestion from the clinical team.
Monogenic hearing loss v2.42 MN1 Arina Puzriakova Gene: mn1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.41 MN1 Arina Puzriakova gene: MN1 was added
gene: MN1 was added to Hearing loss. Sources: Literature
for-review tags were added to gene: MN1.
Mode of inheritance for gene: MN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MN1 were set to 31834374; 31839203
Phenotypes for gene: MN1 were set to CEBALID syndrome, 618774
Review for gene: MN1 was set to GREEN
Added comment: Associated with phenotype in OMIM, and a probable gene for MN1 C-terminal truncation syndrome in G2P.

Over 20 unrelated probands reported with heterozygous MN1 truncating variants, associated with a distinct phenotype which includes DD, craniofacial abnormalities, and structural abnormalities in the brain (e.g. polymicrogyria, dysmorphic corpus callosum and anomalies of the cerebellum). 20/25 individuals had conductive and/or sensorineural hearing loss (no report on hearing status in a further 6 individuals across the two studies).

Most variants cluster in the C-terminal, and all were predicted to escape NMD. Authors postulated that the resulting truncated protein may have a dominant-negative or gain-of-function effect.
Sources: Literature
Monogenic hearing loss v2.40 YARS Sarah Leigh commented on gene: YARS: The new gene for YARS is YARS1
Monogenic hearing loss v2.40 YARS Sarah Leigh Tag watchlist tag was added to gene: YARS.
Monogenic hearing loss v2.40 YARS Sarah Leigh Classified gene: YARS as Amber List (moderate evidence)
Monogenic hearing loss v2.40 YARS Sarah Leigh Gene: yars has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.39 YARS Sarah Leigh Added comment: Comment on phenotypes: Monoallelic variants are associated with Charcot-Marie-Tooth disease, dominant intermediate C 608323, while biallelic variants are associated with a complex phenotype that may include intellectual disability, hearing loss and liver damage.
Monogenic hearing loss v2.39 YARS Sarah Leigh Phenotypes for gene: YARS were changed from Charcot-Marie-Tooth disease, dominant intermediate C 608323; Intellectual disability; deafness; nystagmus; liver dysfunction to Charcot-Marie-Tooth disease, dominant intermediate C 608323; Intellectual disability; deafness; nystagmus; liver dysfunction
Monogenic hearing loss v2.38 YARS Sarah Leigh gene: YARS was added
gene: YARS was added to Hearing loss. Sources: Literature
new-gene-name tags were added to gene: YARS.
Mode of inheritance for gene: YARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YARS were set to 30304524; 29232904; 27633801
Phenotypes for gene: YARS were set to Charcot-Marie-Tooth disease, dominant intermediate C 608323; Intellectual disability; deafness; nystagmus; liver dysfunction
Review for gene: YARS was set to AMBER
Added comment: Biallelic variants in three families with complex clinical conditions including developmental delay. PMID 30304524 reports an extended family with microcephaly, expressive language delay, hearing loss, amongst other features. PMID 29232904 reports a proband whose phenotype included hearing loss, retnititis pigmentosa and hypotonia, but did not include intellectual disability. PMID 27633801 reports two sibblings with hypotionia, the older brother at 15 years of age has mild delays, he attends school on an individualized educational program and functions at a grade 3 level, but not hearing loss was reported.
Sources: Literature
Monogenic hearing loss v2.37 CNRIP1 Eleanor Williams changed review comment from: PMID: 32337552 - ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature; to: PMID: 32337552 - Lezirovitz et al 2020 ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Monogenic hearing loss v2.37 PPP3R1 Eleanor Williams gene: PPP3R1 was added
gene: PPP3R1 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: PPP3R1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP3R1 were set to 32337552; 19159392
Phenotypes for gene: PPP3R1 were set to Deafness, autosomal dominant 58 MIM#615654
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Monogenic hearing loss v2.36 PLEK Eleanor Williams gene: PLEK was added
gene: PLEK was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: PLEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLEK were set to 32337552; 19159392
Phenotypes for gene: PLEK were set to Deafness, autosomal dominant 58 MIM#615654
Added comment: PMID: 32337552 - Lezirovitz et al 2020- ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Monogenic hearing loss v2.35 CNRIP1 Eleanor Williams gene: CNRIP1 was added
gene: CNRIP1 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: CNRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CNRIP1 were set to 32337552; 19159392
Phenotypes for gene: CNRIP1 were set to Deafness, autosomal dominant 58 MIM#615654
Review for gene: CNRIP1 was set to RED
Added comment: PMID: 32337552 - ~200 Kb genomic duplication in 2p14 was found that segregates with postlingual progressive sensorineural autosomal dominant hearing loss in a large Brazilian family with 20 affected individuals (the reported DFNA58 family from PMID: 19159392). The duplication covers PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), as well as four uncharacterized long non-coding RNA genes and part of a novel protein-coding gene. Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea and CNRIP1 mRNA was overexpressed in affected family members.
Sources: Literature
Monogenic hearing loss v2.34 ABCC1 Eleanor Williams Classified gene: ABCC1 as Amber List (moderate evidence)
Monogenic hearing loss v2.34 ABCC1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber based on expert review and some cases reported.
Monogenic hearing loss v2.34 ABCC1 Eleanor Williams Gene: abcc1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.33 ABCC1 Eleanor Williams Phenotypes for gene: ABCC1 were changed from Nonsyndromic hearing loss to Nonsyndromic hearing loss; ?Deafness, autosomal dominant 77, 618915
Monogenic hearing loss v2.32 ABCC1 Eleanor Williams commented on gene: ABCC1
Monogenic hearing loss v2.32 HOMER2 Eleanor Williams Classified gene: HOMER2 as Amber List (moderate evidence)
Monogenic hearing loss v2.32 HOMER2 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. Two families with monoallelic variants, and a mouse with biallelic variants and deafness. Heterozygous mice did not show hearing loss so promoting to amber not green just now. Genomics England clinical team support this rating.
Monogenic hearing loss v2.32 HOMER2 Eleanor Williams Gene: homer2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.31 ELMOD3 Eleanor Williams Phenotypes for gene: ELMOD3 were changed from ?Deafness, autosomal recessive 88, 615429 to ?Deafness, autosomal recessive 88, 615429; Deafness, autosomal dominant
Monogenic hearing loss v2.30 ELMOD3 Eleanor Williams Publications for gene: ELMOD3 were set to
Monogenic hearing loss v2.29 ELMOD3 Eleanor Williams Mode of inheritance for gene: ELMOD3 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.28 ELMOD3 Eleanor Williams Classified gene: ELMOD3 as Amber List (moderate evidence)
Monogenic hearing loss v2.28 ELMOD3 Eleanor Williams Added comment: Comment on list classification: Although there are 2 SNV cases plus a mouse model the mode of inheritance differs. In another case there is a multigene deletion. Promoting from red to amber for now, and will wait for further cases to determine clarity on the mode of inheritance. Amber rating supported by the Genomics England clinical team.
Monogenic hearing loss v2.28 ELMOD3 Eleanor Williams Gene: elmod3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.27 DMXL2 Eleanor Williams Tag for-review tag was added to gene: DMXL2.
Monogenic hearing loss v2.27 DMXL2 Eleanor Williams Classified gene: DMXL2 as Amber List (moderate evidence)
Monogenic hearing loss v2.27 DMXL2 Eleanor Williams Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Monogenic hearing loss v2.27 DMXL2 Eleanor Williams Gene: dmxl2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.26 DMXL2 Eleanor Williams Phenotypes for gene: DMXL2 were changed from Sensorineural Hearing Loss; ORPHA90636; OMIM:612186 to ?Deafness, autosomal dominant 71, 617605; Epileptic encephalopathy, early infantile, 81, 618663
Monogenic hearing loss v2.25 DMXL2 Eleanor Williams Publications for gene: DMXL2 were set to 27657680; 22875945; 25248098
Monogenic hearing loss v2.24 DMXL2 Eleanor Williams Added comment: Comment on mode of inheritance: updating to both monoallelic and biallelic, as deafness with both type of inheritance are reported, although more with biallelic
Monogenic hearing loss v2.24 DMXL2 Eleanor Williams Mode of inheritance for gene: DMXL2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.23 DMXL2 Eleanor Williams edited their review of gene: DMXL2: Added comment: After consultation with Genomics England clinical team it has been decided to rate this gene green as, although hearing loss presents with epileptic encephalopathy, hearing loss is a consistent and early feature.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.23 HARS2 Eleanor Williams Tag for-review tag was added to gene: HARS2.
Monogenic hearing loss v2.23 HARS2 Eleanor Williams Classified gene: HARS2 as Amber List (moderate evidence)
Monogenic hearing loss v2.23 HARS2 Eleanor Williams Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review
Monogenic hearing loss v2.23 HARS2 Eleanor Williams Gene: hars2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.22 EPS8L2 Eleanor Williams Tag for-review tag was added to gene: EPS8L2.
Monogenic hearing loss v2.22 EPS8L2 Eleanor Williams Classified gene: EPS8L2 as Amber List (moderate evidence)
Monogenic hearing loss v2.22 EPS8L2 Eleanor Williams Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review
Monogenic hearing loss v2.22 EPS8L2 Eleanor Williams Gene: eps8l2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.21 COL4A6 Eleanor Williams Tag for-review tag was added to gene: COL4A6.
Monogenic hearing loss v2.21 CDC14A Eleanor Williams Tag for-review tag was added to gene: CDC14A.
Monogenic hearing loss v2.21 CDC14A Eleanor Williams Classified gene: CDC14A as Amber List (moderate evidence)
Monogenic hearing loss v2.21 CDC14A Eleanor Williams Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review
Monogenic hearing loss v2.21 CDC14A Eleanor Williams Gene: cdc14a has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.20 AIFM1 Eleanor Williams Tag for-review tag was added to gene: AIFM1.
Monogenic hearing loss v2.20 AIFM1 Eleanor Williams Classified gene: AIFM1 as Amber List (moderate evidence)
Monogenic hearing loss v2.20 AIFM1 Eleanor Williams Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review
Monogenic hearing loss v2.20 AIFM1 Eleanor Williams Gene: aifm1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v2.19 USP48 Eleanor Williams Tag watchlist tag was added to gene: USP48.
Monogenic hearing loss v2.19 USP48 Eleanor Williams changed review comment from: ESHG2020 - C06.2 - Whole Exome Sequencing, Molecular Assays, Immunohistology and Animal Models associate USP48 to Hereditary Hearing Loss - Bassani et al. Report 1 large Italian family, and 2 unrelated Dutch families with non-syndromic hearing loss and potentially pathogenic missense variants in USP48. A 4th case with unilateral cochlear nerve aplasia and a de novo splice variant in the same gene is reported. A zebrafish knockout for the USP48 paralog showed delayed primary motoneurons development and behaviour indicative of vestibular dysfunction and hearing impairment and acoustic startle response assays revealed a reduced auditory response.
No publication relating to this work could be found in PubMed at this time.
Sources: Literature; to: Conference talk/abstract from ESHG2020 - C06.2 - Whole Exome Sequencing, Molecular Assays, Immunohistology and Animal Models associate USP48 to Hereditary Hearing Loss - Bassani et al. Report 1 large Italian family, and 2 unrelated Dutch families with non-syndromic hearing loss and potentially pathogenic missense variants in USP48. A 4th case with unilateral cochlear nerve aplasia and a de novo splice variant in the same gene is reported. A zebrafish knockout for the USP48 paralog showed delayed primary motoneurons development and behaviour indicative of vestibular dysfunction and hearing impairment and acoustic startle response assays revealed a reduced auditory response.
No publication relating to this work could be found in PubMed at this time.
Sources: Literature
Monogenic hearing loss v2.19 USP48 Eleanor Williams gene: USP48 was added
gene: USP48 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: USP48 was set to Unknown
Phenotypes for gene: USP48 were set to non-syndromic hearing loss
Review for gene: USP48 was set to RED
Added comment: ESHG2020 - C06.2 - Whole Exome Sequencing, Molecular Assays, Immunohistology and Animal Models associate USP48 to Hereditary Hearing Loss - Bassani et al. Report 1 large Italian family, and 2 unrelated Dutch families with non-syndromic hearing loss and potentially pathogenic missense variants in USP48. A 4th case with unilateral cochlear nerve aplasia and a de novo splice variant in the same gene is reported. A zebrafish knockout for the USP48 paralog showed delayed primary motoneurons development and behaviour indicative of vestibular dysfunction and hearing impairment and acoustic startle response assays revealed a reduced auditory response.
No publication relating to this work could be found in PubMed at this time.
Sources: Literature
Monogenic hearing loss v2.18 SLC12A2 Zornitza Stark reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32294086; Phenotypes: Congenital, severe to profound hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v2.18 DMD Sarah Leigh Tag Skewed X-inactivation tag was added to gene: DMD.
Monogenic hearing loss v2.18 SLC52A3 Eleanor Williams Tag for-review tag was added to gene: SLC52A3.
Monogenic hearing loss v2.18 SLC52A2 Eleanor Williams Tag for-review tag was added to gene: SLC52A2.
Monogenic hearing loss v2.18 SLC52A2 Eleanor Williams Tag treatable tag was added to gene: SLC52A2.
Monogenic hearing loss v2.18 SLC52A2 Eleanor Williams Classified gene: SLC52A2 as Green List (high evidence)
Monogenic hearing loss v2.18 SLC52A2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. More than 3 cases reported in patients with Brown-Vialetto-Van Laere syndrome 2 and variants in this gene. Expert reviewer reports that hearing loss may be the first presentation.
Monogenic hearing loss v2.18 SLC52A2 Eleanor Williams Gene: slc52a2 has been classified as Green List (High Evidence).
Monogenic hearing loss v2.17 SLC52A2 Eleanor Williams Phenotypes for gene: SLC52A2 were changed from to Brown-Vialetto-Van Laere syndrome 2 #614707
Monogenic hearing loss v2.16 SLC52A2 Eleanor Williams Publications for gene: SLC52A2 were set to
Monogenic hearing loss v2.15 SLC52A2 Eleanor Williams Mode of inheritance for gene: SLC52A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.14 SLC52A2 Eleanor Williams edited their review of gene: SLC52A2: Changed publications: 22740598, 22864630, 23243084, 24253200; Changed phenotypes: Brown-Vialetto-Van Laere syndrome 2 #614707
Monogenic hearing loss v2.14 SLC52A2 Eleanor Williams edited their review of gene: SLC52A2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.14 SLC52A2 Eleanor Williams commented on gene: SLC52A2: Associated with Brown-Vialetto-Van Laere syndrome 2 #614707 (AR) in OMIM. Early childhood onset of sensorineural deafness is a feature along with bulbar dysfunction, and severe diffuse muscle weakness and wasting of the upper and lower limbs and axial muscles, resulting in respiratory insufficiency.

Numerous cases have been reported with variants in the SLC52A2 gene and Brown-Vialetto-Van Laere syndrome 2:

PMID: 22740598 Johnson et al 2012 - used linkage and exome sequencing to identify a novel mutation (p.G306R (c.916G>A)) in SLC52A2 in an extended Lebanese Brown-Vialetto-Van Laere kindred. The same homozygous mutation was identified in one additional subject from the UK, from 44 screened.

PMID: 22864630 Haack et al 2012 - exome sequencing of a single case with Brown-Vialetto-Van Laere syndrome showed compound heterozygosity for two pathogenic mutations in the SLC52A2 gene. Overexpression studies confirmed that the gene products of both mutant alleles have reduced riboflavin transport activities.

PMID: 23243084 Ciccolella et al 2013 - 1 case of a severe BVVL patient with two novel compound heterozygous mutations in SLC52A2 (c.155C>T, p.S52F and c.1255G>A, p.G419S). Functional studies show that these variants impair the gene expression of the corresponding transporter, resulting in a significant reduction of riboflavin transport.

PMID: 24253200 Foley et al 2014 - using exome and sanger sequencing identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy, hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression.
Monogenic hearing loss v2.14 SLC52A3 Eleanor Williams Phenotypes for gene: SLC52A3 were changed from to Brown-Vialetto-Van Laere syndrome 1 #211530
Monogenic hearing loss v2.13 SLC52A3 Eleanor Williams Publications for gene: SLC52A3 were set to
Monogenic hearing loss v2.12 SLC52A3 Eleanor Williams edited their review of gene: SLC52A3: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.12 SLC52A3 Eleanor Williams Tag treatable tag was added to gene: SLC52A3.
Monogenic hearing loss v2.12 SLC52A3 Eleanor Williams Mode of inheritance for gene: SLC52A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.11 SLC52A3 Eleanor Williams Classified gene: SLC52A3 as Green List (high evidence)
Monogenic hearing loss v2.11 SLC52A3 Eleanor Williams Added comment: Comment on list classification: More than 3 cases reported with variants in SLC52A3 in patients Brown-Vialetto-van Laere syndrome. Sensorineural deafness is a feature of this syndrome and often presents first.
Monogenic hearing loss v2.11 SLC52A3 Eleanor Williams Gene: slc52a3 has been classified as Green List (High Evidence).
Monogenic hearing loss v2.10 SLC52A3 Eleanor Williams commented on gene: SLC52A3: Associated with Brown-Vialetto-Van Laere syndrome 1 #211530 (AR) in OMIM, a form of progressive bulbar palsy with sensorineural deafness.

Multiple cases of variants in this gene have been found in patients with Brown-Vialetto-Van Laere syndrome 1:

PMID: 20206331 Green et al 2010 - identified homozygous or compound heterozygous variants in C20orf54 (SLC52A3) in individuals with Brown-Vialetto-Van Laere syndrome from 7 families of European, Pakistani and Arabic ancestry. Nonsense and missense variants were found. Used homozgyosity mapping in the first family and then candidate gene analysis. They also report that 58 cases have been documented in the literature, with the age at onset ranged from infancy to early in the third decade, with the majority presenting in the second decade. Hearing loss preceded the onset of neurological signs in most cases. C20ORF54 is thought to play a role in riboflavin transport.

PMID: 20920669 Johnson et al 2010 - performed exome sequencing in patients with Brown-Vialetto-van Laere syndrome. In one patient in common with Green et al 2010 they found compound heterozygous variants in C20orf54 (patient 2008-410) rather than the homozygous variant Green et al reported (case 4). The results were confirmed by Sanger sequence and the parents were found to each have 1 heterozygous variant. They also report an additional family (DZ) from Eastern Turkey with a homozygous variant in affected individuals.
Monogenic hearing loss v2.10 SLC52A3 Eleanor Williams gene: SLC52A3 was added
gene: SLC52A3 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: SLC52A3 was set to Unknown
Added comment: Gene suggested for panel by Dr Julia Rankin (Royal Devon and Exeter NHS Foundation Trust). Sensorineural deafness is the presenting feature in cases presenting after infancy with other neurology a year or 2 later – treatment with Riboflavin can be effective.
Sources: Expert list
Monogenic hearing loss v2.9 SLC52A2 Eleanor Williams changed review comment from: Gene suggested for panel by Dr Julia Rankin (Royal Devon and Exeter NHS Foundation Trust)
Sources: Expert list; to: Gene suggested for panel by Dr Julia Rankin (Royal Devon and Exeter NHS Foundation Trust). Sensorineural deafness is the presenting feature in cases presenting after infancy with other neurology a year or 2 later – treatment with Riboflavin can be effective.
Sources: Expert list
Monogenic hearing loss v2.9 SLC52A2 Eleanor Williams gene: SLC52A2 was added
gene: SLC52A2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: SLC52A2 was set to Unknown
Added comment: Gene suggested for panel by Dr Julia Rankin (Royal Devon and Exeter NHS Foundation Trust)
Sources: Expert list
Monogenic hearing loss v2.8 FOXF2 Zornitza Stark gene: FOXF2 was added
gene: FOXF2 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: FOXF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOXF2 were set to 30561639; 22022403
Phenotypes for gene: FOXF2 were set to profound sensorineural hearing loss (SNHL); cochlea malformations; incomplete partition type I anomaly of the cochlea
Review for gene: FOXF2 was set to AMBER
Added comment: Single family: variant has functional data to demonstrate effect on protein, plus mouse model supports gene-disease association.
Sources: Literature
Monogenic hearing loss v2.8 ABCC1 Zornitza Stark gene: ABCC1 was added
gene: ABCC1 was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: ABCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABCC1 were set to 31273342
Phenotypes for gene: ABCC1 were set to Nonsyndromic hearing loss
Review for gene: ABCC1 was set to AMBER
Added comment: Total of 3 variants reported in 3 families with post lingual ADSNHL, including 1 which segregates in a large family (10 affected)

The variant identified in the large multiplex family is present in gnomAD (10 hets), but onset noted to be in 2nd or 3rd decade of life. Functional studies performed. Other 2 variants reported absent in gnomAD. In light of gnomad frequency of one of the variants, suggest Amber rating.
Sources: Literature
Monogenic hearing loss v2.8 MITF Ellen McDonagh commented on gene: MITF: There is evidence to suggest there is reduced penetrance for this gene-disease association (PMID: 26100139). Due to feedback from Rowenna Roberts at GOSH, this gene has therefore been denoted as having incomplete pentrance.
Monogenic hearing loss v2.8 MITF Ellen McDonagh Publications for gene: MITF were set to 10578055; 10587587; 10760582; 10851256; 10942418; 11331755; 11929831; 11929848; 11930005; 12032083; 12086670; 12093801; 12235125; 12668617; 13985019; 15254223; 15623583; 15716956; 16001072; 16140982; 16998588; 17182868; 18316599; 18510545; 19188590; 22012259; 22080950; 26168401; 666627; 7874158; 7874167; 7874168; 8069297; 8578601; 8589691; 8659547; 8782819; 9158138; 9499424; 9500554; 9546825; 9677380; 9856573; 27889061
Monogenic hearing loss v2.7 MITF Ellen McDonagh Source Expert was removed from MITF.
Penetrance for gene MITF was set from to Complete
Monogenic hearing loss v2.6 Eleanor Williams Panel version has been signed off
Monogenic hearing loss v2.4 SOX2 Zornitza Stark reviewed gene: SOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30262714, 16932809, 16145681; Phenotypes: Microphthalmia, syndromic 3, MIM# 206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v2.4 SNAI2 Zornitza Stark reviewed gene: SNAI2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12444107, 30936914; Phenotypes: Waardenburg syndrome, type 2D, MIM# 608890; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v2.4 SLITRK6 Zornitza Stark reviewed gene: SLITRK6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23543054, 29551497; Phenotypes: Deafness and myopia, MIM#221200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v2.4 SIX5 Zornitza Stark reviewed gene: SIX5: Rating: RED; Mode of pathogenicity: None; Publications: 17357085, 24429398, 21280147, 14704431, 17357085, 11950062; Phenotypes: Branchiootorenal syndrome 2, MIM#610896; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v2.4 PMP22 Zornitza Stark reviewed gene: PMP22: Rating: AMBER; Mode of pathogenicity: None; Publications: 8355122, 10330345, 12578939; Phenotypes: Charcot-Marie-Tooth disease, type 1E 118300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v2.4 FOXI1 Zornitza Stark reviewed gene: FOXI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29242249, 9843211, 17503324; Phenotypes: Enlarged vestibular aqueduct 600791, deafness, renal tubular acidosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v2.4 FDXR Zornitza Stark gene: FDXR was added
gene: FDXR was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 28965846
Phenotypes for gene: FDXR were set to Auditory neuropathy and optic atrophy, MIM# 617717
Review for gene: FDXR was set to GREEN
gene: FDXR was marked as current diagnostic
Added comment: 8 individuals from 4 unrelated families reported, onset of symptoms in first/second decades.
Sources: Expert list
Monogenic hearing loss v2.4 ESRP1 Zornitza Stark gene: ESRP1 was added
gene: ESRP1 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: ESRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESRP1 were set to 29107558
Phenotypes for gene: ESRP1 were set to Deafness, autosomal recessive 109, MIM# 618013
Review for gene: ESRP1 was set to AMBER
Added comment: Single family reported with affected sibs, mouse model. Amber or Red.
Sources: Expert list
Monogenic hearing loss v2.4 COL9A1 Zornitza Stark reviewed gene: COL9A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Stickler syndrome, type IV, MIM#614134; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v2.4 COL2A1 Zornitza Stark reviewed gene: COL2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27408751; Phenotypes: Stickler syndrome, type I, MIM108300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Monogenic hearing loss v2.4 COL11A1 Zornitza Stark reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30245514; Phenotypes: Stickler syndrome, type II, MIM#604841, Deafness, autosomal dominant 37, MIM#618533; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Monogenic hearing loss v2.4 CISD2 Zornitza Stark reviewed gene: CISD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25371195; Phenotypes: Wolfram syndrome 2, MIM# 604928; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v2.4 HOMER2 Eleanor Williams changed review comment from: Provisional association with ?Deafness, autosomal dominant 68 #616707 (AD) in OMIM.

2 families reported:
PMID: 25816005 - Azaiez et al 2015 - one family with post-lingual progressive autosomal dominant non-syndromic hearing loss and a missense variant p.Arg185Pro in HOMER2
PMID: 30047143 - Lue et al 2018 - Chinese family with autosomal dominant, non-syndromic hearing loss and a pathogenic variant c.840_841insC in HOMER2 that leads to a premature stop codon).

Azaiez et al 2015 also report mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss.; to: Provisional association with ?Deafness, autosomal dominant 68 #616707 (AD) in OMIM.

2 families reported:
PMID: 25816005 - Azaiez et al 2015 - one family with post-lingual progressive autosomal dominant non-syndromic hearing loss and a missense variant p.Arg185Pro in HOMER2
PMID: 30047143 - Lue et al 2018 - Chinese family with autosomal dominant, non-syndromic hearing loss and a pathogenic variant c.840_841insC in HOMER2 that leads to a premature stop codon).

Azaiez et al 2015 also report mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss. Age-matched WT and Homer2 +/- animals showed no differences in electrophysiological hearing tests.
Monogenic hearing loss v2.4 HOMER2 Eleanor Williams reviewed gene: HOMER2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v2.4 HARS2 Eleanor Williams edited their review of gene: HARS2: Added comment: 6 new cases, so now 8 independent cases, which is sufficient to rate green.

New cases:

PMID: 31827252 - Demain et al 2019 - 3 unrelated families each with compound heterozygous variants in HARS2 in affected members. All 3 families share the c.1439G>A p.(Arg480His) (NM_012208.3) variant along with other likely pathogenic variants.

PMID: 31449985 - Karstensen et al 2019 - three novel families, compound heterozygous for missense variants in HARS2 and early onset, rapidly progressive hearing impairment in the five affected individuals. Premature ovarian insufficiency was also seen in some individuals.; Changed rating: GREEN
Monogenic hearing loss v2.4 EPS8L2 Eleanor Williams reviewed gene: EPS8L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v2.4 ELMOD3 Eleanor Williams reviewed gene: ELMOD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v2.4 DMXL2 Eleanor Williams reviewed gene: DMXL2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27657680, 31688942; Phenotypes: ?Deafness, autosomal dominant 71, 617605; Mode of inheritance: None
Monogenic hearing loss v2.4 COL4A6 Eleanor Williams edited their review of gene: COL4A6: Changed rating: RED
Monogenic hearing loss v2.4 COL4A6 Eleanor Williams changed review comment from: Provisionally associated with ?Deafness, X-linked 6 #300914 (XLR) in OMIM.
Only 1 family reported in PMID: 23714752 - Rost et al 2014 -  a Hungarian three-generation family with X-linked nonsyndromic congenital hearing loss with a missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6 in all affected family members. In situ hybridization and immunostaining demonstrated expression of the COL4A6 homologs in the otic vesicle of the zebrafish and in the murine inner ear, supporting its role in normal ear development and function.

Pubmed search didn’t find any other cases.; to: Provisionally associated with ?Deafness, X-linked 6 #300914 (XLR) in OMIM.
Only 1 family reported in PMID: 23714752 - Rost et al 2014 -  a Hungarian three-generation family with X-linked nonsyndromic congenital hearing loss with a missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6 in all affected family members. In situ hybridization and immunostaining demonstrated expression of the COL4A6 homologs in the otic vesicle of the zebrafish and in the murine inner ear, supporting its role in normal ear development and function.

Pubmed search didn’t find any other cases.
Monogenic hearing loss v2.4 COL4A6 Eleanor Williams commented on gene: COL4A6
Monogenic hearing loss v2.4 CDC14A Eleanor Williams reviewed gene: CDC14A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29293958, 27259055; Phenotypes: Deafness, autosomal recessive 32, with or without immotile sperm, 608653; Mode of inheritance: None
Monogenic hearing loss v2.4 AIFM1 Eleanor Williams reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25986071; Phenotypes: Deafness, X-linked 5, 300614; Mode of inheritance: None
Monogenic hearing loss v2.4 KCNQ4 Ellen McDonagh Tag watchlist was removed from gene: KCNQ4.
Monogenic hearing loss v2.4 MITF Ellen McDonagh Tag watchlist was removed from gene: MITF.
Monogenic hearing loss v2.4 WBP2 Zornitza Stark gene: WBP2 was added
gene: WBP2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: WBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP2 were set to 26881968
Phenotypes for gene: WBP2 were set to Deafness, autosomal recessive 107, MIM#617639
Review for gene: WBP2 was set to AMBER
Added comment: Two unrelated families identified in a large cohort; supportive animal model data.
Sources: Expert list
Monogenic hearing loss v2.4 TOP2B Zornitza Stark gene: TOP2B was added
gene: TOP2B was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: TOP2B were set to 31198993
Phenotypes for gene: TOP2B were set to Deafness, autosomal dominant
Added comment: One multigenerational family where variant in this gene segregated with deafness; two additional variants identified in a cohort; supportive animal model data.
Sources: Expert list
Monogenic hearing loss v2.4 TMTC2 Zornitza Stark gene: TMTC2 was added
gene: TMTC2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: TMTC2 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: TMTC2 were set to 29671961; 27311106
Phenotypes for gene: TMTC2 were set to Deafness
Review for gene: TMTC2 was set to AMBER
Added comment: Two unrelated families reported, no functional evidence.
Sources: Expert list
Monogenic hearing loss v2.4 SPNS2 Zornitza Stark gene: SPNS2 was added
gene: SPNS2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: SPNS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPNS2 were set to 30973865; 25356849
Phenotypes for gene: SPNS2 were set to Deafness, autosomal recessive 115, MIM#618457
Review for gene: SPNS2 was set to AMBER
Added comment: Single family reported, mouse model shows progressive hearing loss.
Sources: Expert list
Monogenic hearing loss v2.4 SPATC1L Zornitza Stark gene: SPATC1L was added
gene: SPATC1L was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: SPATC1L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPATC1L were set to 30177775
Phenotypes for gene: SPATC1L were set to Deafness
Added comment: Two families with compound het variants, and one family with heterozygous variant and dominant pattern of inheritance described, some functional data.
Sources: Expert list
Monogenic hearing loss v2.4 ROR1 Zornitza Stark gene: ROR1 was added
gene: ROR1 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: ROR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROR1 were set to 27162350
Phenotypes for gene: ROR1 were set to Deafness, autosomal recessive 108, MIM#617654
Review for gene: ROR1 was set to AMBER
Added comment: Single family, homozygous missense variant in sibs; mouse model.
Sources: Expert list
Monogenic hearing loss v2.4 PPIP5K2 Zornitza Stark gene: PPIP5K2 was added
gene: PPIP5K2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: PPIP5K2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIP5K2 were set to 29590114
Phenotypes for gene: PPIP5K2 were set to Deafness, autosomal recessive 100, MIM#618422
Review for gene: PPIP5K2 was set to AMBER
Added comment: Two apparently unrelated families with multiple affecteds segregating a homozygous missense variant; mouse model.
Sources: Expert list
Monogenic hearing loss v2.4 PLS1 Zornitza Stark gene: PLS1 was added
gene: PLS1 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: PLS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLS1 were set to 31397523; 31432506; 30872814
Phenotypes for gene: PLS1 were set to Deafness
Review for gene: PLS1 was set to GREEN
gene: PLS1 was marked as current diagnostic
Added comment: non-syndromic deafness in 5 families with mono-allelic variants in this gene, and a mouse model.
Sources: Expert list
Monogenic hearing loss v2.4 NARS2 Zornitza Stark reviewed gene: NARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25807530, 28077841, 30327238, 25385316; Phenotypes: Deafness, autosomal recessive 94, MIM#618434, Combined oxidative phosphorylation deficiency 24, MIM#616239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v2.4 MPZL2 Zornitza Stark gene: MPZL2 was added
gene: MPZL2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: MPZL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPZL2 were set to 29982980; 29961571
Phenotypes for gene: MPZL2 were set to Deafness, autosomal recessive 111, MIM#618145
Review for gene: MPZL2 was set to GREEN
Added comment: 16 individuals from 6 unrelated consanguineous families reported with bi-allelic variants in this gene.
Sources: Expert list
Monogenic hearing loss v2.4 LMX1A Zornitza Stark reviewed gene: LMX1A: Rating: AMBER; Mode of pathogenicity: None; Publications: 29754270, 29971487; Phenotypes: Deafness, autosomal recessive and autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.4 HOMER2 Zornitza Stark gene: HOMER2 was added
gene: HOMER2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: HOMER2 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: HOMER2 were set to 25816005; 30047143; 25816005
Phenotypes for gene: HOMER2 were set to Deafness, autosomal dominant 68, MIM#616707
Review for gene: HOMER2 was set to GREEN
gene: HOMER2 was marked as current diagnostic
Added comment: Two families reported and a mouse model.
Sources: Expert list
Monogenic hearing loss v2.4 HARS2 Zornitza Stark reviewed gene: HARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21464306, 27650058, 31827252, 31486067; Phenotypes: Perrault syndrome, deafness, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v2.4 GJB6 Zornitza Stark reviewed gene: GJB6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v2.4 GJB3 Zornitza Stark reviewed gene: GJB3: Rating: RED; Mode of pathogenicity: None; Publications: 9843210; Phenotypes: Deafness, autosomal dominant 2B, MIM#612644; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Monogenic hearing loss v2.4 EPS8L2 Zornitza Stark gene: EPS8L2 was added
gene: EPS8L2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: EPS8L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPS8L2 were set to 26282398; 2391890; 28281779
Phenotypes for gene: EPS8L2 were set to Deafness, autosomal recessive 106, MIM#617637
Review for gene: EPS8L2 was set to GREEN
gene: EPS8L2 was marked as current diagnostic
Added comment: Two unrelated families and a mouse model.
Sources: Expert list
Monogenic hearing loss v2.4 ELMOD3 Zornitza Stark reviewed gene: ELMOD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 240396609, 31628468, 30284680, 29713870; Phenotypes: Deafness, autosomal recessive 88, MIM#615429, Deafness, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v2.4 DMXL2 Zornitza Stark reviewed gene: DMXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31688942; Phenotypes: Epileptic encephalopathy with deafness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Monogenic hearing loss v2.4 COL4A6 Zornitza Stark reviewed gene: COL4A6: Rating: RED; Mode of pathogenicity: None; Publications: 23714752; Phenotypes: Deafness, X-linked 6, MIM#300914; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Monogenic hearing loss v2.4 CDC14A Zornitza Stark gene: CDC14A was added
gene: CDC14A was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: CDC14A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC14A were set to 29293958; 27259055
Phenotypes for gene: CDC14A were set to Deafness, autosomal recessive 32, with or without immotile sperm, MIM#608653
Review for gene: CDC14A was set to GREEN
gene: CDC14A was marked as current diagnostic
Added comment: Multiple affected individuals from unrelated families reported, plus animal model data. Likely to present with apparently isolated deafness in children.
Sources: Expert list
Monogenic hearing loss v2.4 AIFM1 Zornitza Stark gene: AIFM1 was added
gene: AIFM1 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AIFM1 were set to 25986071
Phenotypes for gene: AIFM1 were set to Deafness, X-linked 5, MIM#300614
Review for gene: AIFM1 was set to GREEN
Added comment: More than 10 unrelated families described.
Sources: Expert list
Monogenic hearing loss v2.4 PIK3C2A Eleanor Williams gene: PIK3C2A was added
gene: PIK3C2A was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3C2A were set to 31034465
Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome 618440
Review for gene: PIK3C2A was set to AMBER
Added comment: Associated with Oculoskeletodental syndrome 618440 (AR) in OMIM based on evidence from PMID: 31034465 - Tiosano et al 2019 - report 5 individuals from 3 unrelated consanguineous families with a similar set of clinical features including dysmorphic facial features, short stature, skeletal and neurological abnormalities, and cataracts. 3 out 5 indviduals (one from each family) showed hearing loss (non-progressive hearing deficiency, bilateral moderate conductive hearing loss and sensorineural hearing loss, hearing aids at 22 years old). Homozygous loss-of-function mutations in PIK3C2A were identified in each family.
Sources: Literature
Monogenic hearing loss v2.3 TMEM132E Eleanor Williams Tag watchlist tag was added to gene: TMEM132E.
Monogenic hearing loss v2.3 TMEM132E Eleanor Williams edited their review of gene: TMEM132E: Changed rating: AMBER
Monogenic hearing loss v2.3 TMEM132E Eleanor Williams gene: TMEM132E was added
gene: TMEM132E was added to Hearing loss. Sources: Literature
Mode of inheritance for gene: TMEM132E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM132E were set to 25331638; 31656313
Phenotypes for gene: TMEM132E were set to Nonsyndromic Hearing Loss
Review for gene: TMEM132E was set to RED
Added comment: Two publications support the addition of this gene to the panel:

PMID: 25331638 - Li et al 2015 - report two siblings with prelingual, bilateral, severe to profound sensorineural hearing loss in a consanguineous Chinese family. Whole‐exome sequencing revealed a homozygous missense mutation c.1259G>A (rs139895222), p.Arg420Gln, in TMEM132E that cosegregates with deafness in the family. The parents and a brother were heterozygous. The 1259A allele was not found in 500 ethnically matched controls. Immunofluorescence staining of the Organ of Corti showed Tmem132e highly expressed in murine inner hair cells and knockdown of the tmem132e ortholog in zebrafish affected the mechanotransduction of hair cells. Wild‐type human TMEM132E mRNA, but not the mRNA carrying the c.1259G>A mutation rescued the Tmem132e knockdown phenotype.

PMID: 31656313 - Liaqat et al 2019 - a family of Pakistani origin with prelingual profound sensorineural hearing impairment displaying AR mode of inheritance was investigated via exome and Sanger sequencing. Compound heterozygous variants c.382G>T: p.(Ala128Ser) and c.2204C>T: p.(Pro735Leu) in TMEM132E were observed in affected but not in unaffected family members.
Sources: Literature
Monogenic hearing loss v2.2 HARS Louise Daugherty Tag new-gene-name tag was added to gene: HARS.
Monogenic hearing loss v2.2 HARS Louise Daugherty commented on gene: HARS
Monogenic hearing loss v2.2 KARS Louise Daugherty Tag new-gene-name tag was added to gene: KARS.
Monogenic hearing loss v2.2 KARS Louise Daugherty commented on gene: KARS
Monogenic hearing loss v2.1 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Monogenic hearing loss v2.0 Ellen McDonagh promoted panel to version 2.0
Monogenic hearing loss v1.128 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Monogenic hearing loss v1.124 Eleanor Williams List of related panels changed from Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe) to Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe); R67
Monogenic hearing loss v1.123 GJB2 Eleanor Williams Publications for gene: GJB2 were set to PMID:10218527; 10369869; 10376574; 10422812; 10544226; 10607953; 10633133; 10633135; 10713883; 10757647; 10782932; 10807696; 10830906; 10874298; 10903123; 10980526; 10981905; 10982180; 10982182; 11134236; 11179004; 11298683; 11313751; 11313763; 11354642; 11483639; 11556849; 11746015; 11807148; 11912510; 11935342; 11977173; 12072059; 12080392; 12081719; 12107817; 12111646; 12121355; 12121617; 12172392; 12172394; 12176036; 12189487; 12189493; 12239718; 12372058; 12384501; 12384781; 12457154; 12484567; 12522556; 12548749; 12560944; 12668604; 12684873; 12700168; 12752120; 12786758; 12786762; 12833397; 12865758; 12920081; 1324944; 1370487; 14070830; 14505035; 14694360; 14700667; 14735592; 14985372; 14986832; 15150777; 15151513; 15235031; 15241677; 15253766; 15365987; 15482471; 15592461; 15633193; 15666300; 15700112; 15952212; 15996214; 16059934; 16088916; 16222667; 16380907; 16628254; 16650079; 16773579; 16840571; 16868655; 17036313; 17041943; 17256794; 17330861; 17426645; 17505205; 17660464; 17713529; 17935238; 17993581; 1849321; 18843290; 18925674; 18941476; 18985073; 19050930; 19340074; 19375528; 1964417; 20236118; 20412116; 20442751; 20815033; 21776002; 22031297; 22981120; 25262649; 2706105; 2956987; 8789457; 8978770; 9139825; 9285800; 9326398; 9328482; 9336442; 9358053; 9422505; 9471561; 9482292; 9482297; 9529365; 9620796; 9716127; 9819448; 9856479
Monogenic hearing loss v1.122 DIAPH1 Eleanor Williams changed review comment from: Comment on list classification: Upgrading from red to green after discussion with the GMS musculoskeletal specialist test group in a Webex on 2019-05-13 and consultation with the Genomics England clinical team; to: Comment on list classification: Upgrading from red to green after discussion with the GMS hearing loss specialist test group in a Webex and consultation with the Genomics England clinical team
Monogenic hearing loss v1.122 GJB2 Eleanor Williams edited their review of gene: GJB2: Added comment: Adding publication PMID: 31160754 Shen et al 2019 Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel as additional information.; Changed rating: AMBER; Changed publications: 31160754
Monogenic hearing loss v1.122 ATP2B2 Eleanor Williams Classified gene: ATP2B2 as Amber List (moderate evidence)
Monogenic hearing loss v1.122 ATP2B2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on HI, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.
Monogenic hearing loss v1.122 ATP2B2 Eleanor Williams Gene: atp2b2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.121 ATP2B2 Eleanor Williams Phenotypes for gene: ATP2B2 were changed from to {Deafness, autosomal recessive 12, modifier of} 601386
Monogenic hearing loss v1.120 ATP2B2 Eleanor Williams Added comment: Comment on publications: PMID: 17234811 - Ficarella et al 2007 - A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness.
Monogenic hearing loss v1.120 ATP2B2 Eleanor Williams Publications for gene: ATP2B2 were set to 30535804
Monogenic hearing loss v1.119 ATP2B2 Eleanor Williams Publications for gene: ATP2B2 were set to
Monogenic hearing loss v1.118 ATP2B2 Eleanor Williams Added comment: Comment on mode of inheritance: The 5 cases described in PMID: 30535804 show a monoallelic pattern of inheritance
Monogenic hearing loss v1.118 ATP2B2 Eleanor Williams Mode of inheritance for gene: ATP2B2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.117 ATP2B2 Eleanor Williams edited their review of gene: ATP2B2: Added comment: PMID: 30535804 - Smits et al 2019 - report 5 independant cases. Whole exome sequencing in hearing impaired index cases of Dutch and Polish origins revealed five novel heterozygous (predicted to be) loss-of-function variants of ATP2B2. Two variants, c.1963G>T (p.Glu655*) and c.955delG (p.Ala319fs), occurred de novo. Three variants c.397+1G>A (p.?), c.1998C>A (p.Cys666*), and c.2329C>T (p.Arg777*), were identified in families with an autosomal dominant inheritance pattern of hearing impairment. In most cases HI was early onset, but in one individual hearing loss was reported around 55 years. Whole exome sequence (WES) data were analyzed for variants in a panel of 142 genes known to be associated with nonsyndromic hearing impairment (HI) and relatively common syndromic forms of HI. All variants affect exons, or their splice sites, that encode the ortholog of the rat PMCA2 w/a isoform. This isoform is highly abundant in stereocilia of outer hair cells (OHC) and to a lesser extent at the apical surface of inner hair cells of rats.

Although rare CDH23 variants cooccurred with ATP2B2 variants in all five index cases, they state their findings indicate that mono-allelic loss-of-function variants of ATP2B2 are the underlying cause of HI. However, variants in deep intronic regions or promoter regions were not addressed and can, therefore, not be excluded. CNVs of CDH23 can be excluded for the index cases only. They state they cannot exclude a modifying effect of the CDH23 variants on HI in the affected subjects in their study.; Changed publications: 30535804
Monogenic hearing loss v1.117 CLIC5 Eleanor Williams Classified gene: CLIC5 as Amber List (moderate evidence)
Monogenic hearing loss v1.117 CLIC5 Eleanor Williams Added comment: Comment on list classification: Downgrading the rating from green to amber as upon review there was only 1 case, plus some functional data from mouse.
Monogenic hearing loss v1.117 CLIC5 Eleanor Williams Gene: clic5 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.114 GJB6 Eleanor Williams Classified gene: GJB6 as Amber List (moderate evidence)
Monogenic hearing loss v1.114 GJB6 Eleanor Williams Added comment: Comment on list classification: After consideration by the Genomics England rare disease clinical team it was decided to rate this gene Amber until there is further evidence for the role of SNVs in this gene causing hearing loss.
Monogenic hearing loss v1.114 GJB6 Eleanor Williams Gene: gjb6 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.113 HGF Eleanor Williams Tag watchlist tag was added to gene: HGF.
Monogenic hearing loss v1.113 HGF Eleanor Williams Classified gene: HGF as Amber List (moderate evidence)
Monogenic hearing loss v1.113 HGF Eleanor Williams Added comment: Comment on list classification: After review with the GMS hearing specialist test group in a Webex on 2019-02-13 and consultation with the Genomics England clinical team it was decided to rate this gene Amber and add a watchlist tag.
Monogenic hearing loss v1.113 HGF Eleanor Williams Gene: hgf has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.112 SLC17A8 Eleanor Williams Classified gene: SLC17A8 as Green List (high evidence)
Monogenic hearing loss v1.112 SLC17A8 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green based on new evidence added.
Monogenic hearing loss v1.112 SLC17A8 Eleanor Williams Gene: slc17a8 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.111 DIAPH1 Eleanor Williams Classified gene: DIAPH1 as Green List (high evidence)
Monogenic hearing loss v1.111 DIAPH1 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green after discussion with the GMS musculoskeletal specialist test group in a Webex on 2019-05-13 and consultation with the Genomics England clinical team
Monogenic hearing loss v1.111 DIAPH1 Eleanor Williams Gene: diaph1 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.110 SIX5 Eleanor Williams Classified gene: SIX5 as Amber List (moderate evidence)
Monogenic hearing loss v1.110 SIX5 Eleanor Williams Added comment: Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS hearing specialist test group Webex on 2019-02-13
Monogenic hearing loss v1.110 SIX5 Eleanor Williams Gene: six5 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.109 GJB2 Eleanor Williams commented on gene: GJB2
Monogenic hearing loss v1.109 HGF Eleanor Williams commented on gene: HGF
Monogenic hearing loss v1.109 SLC17A8 Eleanor Williams Publications for gene: SLC17A8 were set to PMID: 12151341; 18215623; 18674745; 19915548; 9323205
Monogenic hearing loss v1.108 SLC17A8 Eleanor Williams commented on gene: SLC17A8
Monogenic hearing loss v1.108 MT-TS1 Eleanor Williams Publications for gene: MT-TS1 were set to PMID:10094190; 10340654; 10371545; 10545608; 10978361; 11069477; 11175301; 11378827; 12461693; 127819; 14605505; 17659260; 20153673; 6213205; 7219534; 7581383; 7669057; 7987332; 8019558; 8572257; 9450881; 9742104; 9832034
Monogenic hearing loss v1.107 APOPT1 Louise Daugherty Tag new-gene-name tag was added to gene: APOPT1.
Monogenic hearing loss v1.107 APOPT1 Louise Daugherty commented on gene: APOPT1
Monogenic hearing loss v1.107 TSPEAR Eleanor Williams Publications for gene: TSPEAR were set to
Monogenic hearing loss v1.106 TJP2 Eleanor Williams Publications for gene: TJP2 were set to PMID: 10601346; 11018256; 12403786; 12704386; 18172007; 18616530; 20602916; 24614073; 25921221; 7951235; 8824195
Monogenic hearing loss v1.105 HGF Eleanor Williams Publications for gene: HGF were set to PMID:11343646; 11564764; 11565020; 12574630; 1386343; 14556002; 14691191; 1531136; 1535333; 15545993; 17467663; 1824873; 1831266; 1837534; 19188684; 19576567; 2142751; 21988987; 21988988; 22763439; 22763448; 2528952; 2531289; 3276728; 7624797; 7854452; 7854453; 8804995; 8898205
Monogenic hearing loss v1.104 CRYM Eleanor Williams Publications for gene: CRYM were set to PMID:12471561; 1384048; 1478656; 16740909; 9328354
Monogenic hearing loss v1.103 CRYM Eleanor Williams commented on gene: CRYM: I think the Abe et al 2003 publication referred to by Emma Ashton is PMID: 12471561 not PMID 420014
Monogenic hearing loss v1.103 SYNE4 Emma Ashton Deleted their comment
Monogenic hearing loss v1.103 CLIC5 Eleanor Williams commented on gene: CLIC5: Checking with the Genomics England clinical team about the rating of this gene.
Monogenic hearing loss v1.103 CLIC5 Eleanor Williams commented on gene: CLIC5
Monogenic hearing loss v1.103 CLIC5 Alistair Pagnamenta reviewed gene: CLIC5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 24781754, 17021174; Phenotypes: Nonsyndromic sensorineural deafness; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.103 HTRA2 Eleanor Williams Classified gene: HTRA2 as Red List (low evidence)
Monogenic hearing loss v1.103 HTRA2 Eleanor Williams Added comment: Comment on list classification: Demoting from Amber to Red following review by Anna De Burca which notes that hearing loss is only reported in one family, and other phenotypes are more neurological.
Monogenic hearing loss v1.103 HTRA2 Eleanor Williams Gene: htra2 has been classified as Red List (Low Evidence).
Monogenic hearing loss v1.102 GJB6 Eleanor Williams commented on gene: GJB6
Monogenic hearing loss v1.102 SIX5 Eleanor Williams commented on gene: SIX5
Monogenic hearing loss v1.102 DIABLO Eleanor Williams Deleted their comment
Monogenic hearing loss v1.102 TSPEAR Eleanor Williams commented on gene: TSPEAR: After review with the NHS GMS hearing specialist group on 2019-02-13 it was decided to keep this gene red. One case reported in Sloan-Heggen et al 2016 with variants associated with hearing loss. Variants reported in Delmaghani et al. (2012) have since been reported in individuals without hearing loss.
Monogenic hearing loss v1.102 TSPEAR Eleanor Williams commented on gene: TSPEAR
Monogenic hearing loss v1.102 TNC Eleanor Williams Mode of inheritance for gene: TNC was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.101 TNC Eleanor Williams Classified gene: TNC as Amber List (moderate evidence)
Monogenic hearing loss v1.101 TNC Eleanor Williams Added comment: Comment on list classification: Changed rating from red to amber as there are 2 reported cases with plausible pathogenic variants in TNC. No functional data.
Monogenic hearing loss v1.101 TNC Eleanor Williams Gene: tnc has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.100 TNC Eleanor Williams commented on gene: TNC
Monogenic hearing loss v1.100 TNC Eleanor Williams Publications for gene: TNC were set to
Monogenic hearing loss v1.99 TJP2 Eleanor Williams commented on gene: TJP2
Monogenic hearing loss v1.99 RPGR Eleanor Williams commented on gene: RPGR
Monogenic hearing loss v1.99 MIR96 Eleanor Williams Phenotypes for gene: MIR96 were changed from to Deafness, autosomal dominant 50 613074
Monogenic hearing loss v1.98 MIR96 Eleanor Williams Publications for gene: MIR96 were set to
Monogenic hearing loss v1.97 MIR96 Eleanor Williams Mode of inheritance for gene: MIR96 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.96 MIR96 Eleanor Williams Classified gene: MIR96 as Amber List (moderate evidence)
Monogenic hearing loss v1.96 MIR96 Eleanor Williams Added comment: Comment on list classification: After review with the NHS GMS hearing specialist group on 2019-02-13 it was decided to rate this gene as Amber. 2 cases reported by Mencia et al 2009 with variants likely to be pathogenic.
Monogenic hearing loss v1.96 MIR96 Eleanor Williams Gene: mir96 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.95 MIR96 Eleanor Williams commented on gene: MIR96
Monogenic hearing loss v1.95 HARS2 Eleanor Williams Publications for gene: HARS2 were set to PMID:12056811; 15779907; 21464306; 517579; 7755634
Monogenic hearing loss v1.94 HARS2 Eleanor Williams Classified gene: HARS2 as Amber List (moderate evidence)
Monogenic hearing loss v1.94 HARS2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber as there are now 2 independent cases of variants in HARS2 in patients with Perrault syndrome.
Monogenic hearing loss v1.94 HARS2 Eleanor Williams Gene: hars2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.93 HARS2 Eleanor Williams commented on gene: HARS2
Monogenic hearing loss v1.93 HARS Eleanor Williams commented on gene: HARS
Monogenic hearing loss v1.93 DIAPH1 Eleanor Williams commented on gene: DIAPH1
Monogenic hearing loss v1.93 DIABLO Eleanor Williams Publications for gene: DIABLO were set to PMID: 10929711; 10929712; 10972280; 11140637; 11140638; 11242052; 11971981; 15557007; 15814844; 21722859
Monogenic hearing loss v1.92 DIABLO Eleanor Williams Mode of inheritance for gene: DIABLO was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.91 DIABLO Eleanor Williams Classified gene: DIABLO as Amber List (moderate evidence)
Monogenic hearing loss v1.91 DIABLO Eleanor Williams Added comment: Comment on list classification: Changed rating from red to amber as there are now two cases of variants in this gene associated with hearing loss
Monogenic hearing loss v1.91 DIABLO Eleanor Williams Gene: diablo has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.90 DIABLO Eleanor Williams Classified gene: DIABLO as Amber List (moderate evidence)
Monogenic hearing loss v1.90 DIABLO Eleanor Williams Added comment: Comment on list classification: Changed rating from red to amber as there are now two cases of variants in this gene associated with hearing loss
Monogenic hearing loss v1.90 DIABLO Eleanor Williams Gene: diablo has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.89 DIABLO Eleanor Williams commented on gene: DIABLO
Monogenic hearing loss v1.89 CRYM Eleanor Williams commented on gene: CRYM
Monogenic hearing loss v1.89 CEACAM16 Eleanor Williams Publications for gene: CEACAM16 were set to PMID:16139472; 21368133; 7655461
Monogenic hearing loss v1.88 CEACAM16 Eleanor Williams Mode of inheritance for gene: CEACAM16 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.87 CEACAM16 Eleanor Williams Classified gene: CEACAM16 as Green List (high evidence)
Monogenic hearing loss v1.87 CEACAM16 Eleanor Williams Added comment: Comment on list classification: Changed rating from red to green. 3 unrelated cases reported.
Monogenic hearing loss v1.87 CEACAM16 Eleanor Williams Gene: ceacam16 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.86 CEACAM16 Eleanor Williams commented on gene: CEACAM16
Monogenic hearing loss v1.86 CCDC50 Eleanor Williams Publications for gene: CCDC50 were set to PMID:12483295; 14527723; 16803894; 17503326
Monogenic hearing loss v1.85 CCDC50 Eleanor Williams Mode of inheritance for gene: CCDC50 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.84 CCDC50 Eleanor Williams Classified gene: CCDC50 as Green List (high evidence)
Monogenic hearing loss v1.84 CCDC50 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. 3 cases reported in the literature.
Monogenic hearing loss v1.84 CCDC50 Eleanor Williams Gene: ccdc50 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.83 CCDC50 Eleanor Williams commented on gene: CCDC50
Monogenic hearing loss v1.83 BDP1 Eleanor Williams commented on gene: BDP1
Monogenic hearing loss v1.83 ATP2B2 Eleanor Williams commented on gene: ATP2B2
Monogenic hearing loss v1.83 DIAPH3 Eleanor Williams Publications for gene: DIAPH3 were set to PMID: 14767582; 15520414; 18755006; 19457867; 20624953
Monogenic hearing loss v1.82 DIAPH3 Eleanor Williams Classified gene: DIAPH3 as Amber List (moderate evidence)
Monogenic hearing loss v1.82 DIAPH3 Eleanor Williams Added comment: Comment on list classification: Changing the rating from red to amber as there are now 2 reported cases.
Monogenic hearing loss v1.82 DIAPH3 Eleanor Williams Gene: diaph3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.81 DIAPH3 Eleanor Williams commented on gene: DIAPH3
Monogenic hearing loss v1.81 NARS2 Eleanor Williams Publications for gene: NARS2 were set to
Monogenic hearing loss v1.80 NARS2 Eleanor Williams Mode of inheritance for gene: NARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.79 CD164 Eleanor Williams Mode of inheritance for gene: CD164 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.78 CD164 Eleanor Williams Phenotypes for gene: CD164 were changed from to ?Deafness, autosomal dominant 66 616969
Monogenic hearing loss v1.77 CD164 Eleanor Williams Publications for gene: CD164 were set to
Monogenic hearing loss v1.76 KITLG Eleanor Williams Phenotypes for gene: KITLG were changed from to Deafness, autosomal dominant 69, unilateral or asymmetric 616697
Monogenic hearing loss v1.75 KITLG Eleanor Williams Publications for gene: KITLG were set to
Monogenic hearing loss v1.74 KITLG Eleanor Williams Classified gene: KITLG as Amber List (moderate evidence)
Monogenic hearing loss v1.74 KITLG Eleanor Williams Added comment: Comment on list classification: Changing rate from red to amber as there are 2 cases
Monogenic hearing loss v1.74 KITLG Eleanor Williams Gene: kitlg has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v1.73 KITLG Eleanor Williams commented on gene: KITLG
Monogenic hearing loss v1.73 KITLG Eleanor Williams Mode of inheritance for gene: KITLG was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.72 SLC26A5 Eleanor Williams Classified gene: SLC26A5 as Green List (high evidence)
Monogenic hearing loss v1.72 SLC26A5 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as 3 unrelated cases now reported.
Monogenic hearing loss v1.72 SLC26A5 Eleanor Williams Gene: slc26a5 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.71 SLC26A5 Eleanor Williams Publications for gene: SLC26A5 were set to PMC4185121 (PMID: 25262649); PMID:10821263; 11423665; 11867734; 12239568; 12719379; 16086836; 17998209; 18776049; 19492055; 21689600; 23212912; 24164807; 25262649
Monogenic hearing loss v1.70 SLC26A5 Eleanor Williams commented on gene: SLC26A5
Monogenic hearing loss v1.70 SYNE4 Eleanor Williams Classified gene: SYNE4 as Green List (high evidence)
Monogenic hearing loss v1.70 SYNE4 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green as there are 3 unrelated cases
Monogenic hearing loss v1.70 SYNE4 Eleanor Williams Gene: syne4 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.69 SYNE4 Eleanor Williams Publications for gene: SYNE4 were set to
Monogenic hearing loss v1.68 SYNE4 Eleanor Williams Mode of inheritance for gene: SYNE4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.67 SYNE4 Eleanor Williams commented on gene: SYNE4
Monogenic hearing loss v1.67 SLC26A5 Emma Ashton reviewed gene: SLC26A5: Rating: GREEN; Mode of pathogenicity: ; Publications: 24164807, 6824437, 26969326; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.67 SYNE4 Emma Ashton edited their review of gene: SYNE4: Added comment: (Homozygous frameshift, 1 family, both parents confirmed carriers in our lab): Horn et al (2013) PMID 23348741 two families of Iraqi Jewish origin with same 2bp deletion. Masterton et al (2018) PMID 28958982 two siblings in one family homozygous -1G>T.; Changed publications: 23348741, 28958982
Monogenic hearing loss v1.66 S1PR2 Eleanor Williams Classified gene: S1PR2 as Green List (high evidence)
Monogenic hearing loss v1.66 S1PR2 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Variants in 3 independent families reported.
Monogenic hearing loss v1.66 S1PR2 Eleanor Williams Gene: s1pr2 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.65 S1PR2 Eleanor Williams Phenotypes for gene: S1PR2 were changed from to Deafness, autosomal recessive 68 610419
Monogenic hearing loss v1.64 S1PR2 Eleanor Williams Publications for gene: S1PR2 were set to
Monogenic hearing loss v1.63 S1PR2 Eleanor Williams Mode of inheritance for gene: S1PR2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.62 S1PR2 Eleanor Williams Deleted their comment
Monogenic hearing loss v1.62 S1PR2 Eleanor Williams commented on gene: S1PR2: Associated with Deafness, autosomal recessive 68 (MIM 610419) in OMIM.

Three independent reports of variants in this gene associated with hearing loss:
1) 2 consanguineous Pakistani families in Santos-Cortez (2016) PMID 26805784
2) 1 consangiuneous Iranian family in Hofrichter et al (2018) PMID 29776397
3) 1 family from GOSH lab
Monogenic hearing loss v1.62 S1PR2 Eleanor Williams commented on gene: S1PR2
Monogenic hearing loss v1.62 OTOGL Eleanor Williams Mode of inheritance for gene: OTOGL was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.61 OTOGL Eleanor Williams Classified gene: OTOGL as Green List (high evidence)
Monogenic hearing loss v1.61 OTOGL Eleanor Williams Added comment: Comment on list classification: Promoting from red to green as two families reported in PMID: 23122586 plus one reported by GOSH.
Monogenic hearing loss v1.61 OTOGL Eleanor Williams Gene: otogl has been classified as Green List (High Evidence).
Monogenic hearing loss v1.60 OTOGL Eleanor Williams Publications for gene: OTOGL were set to
Monogenic hearing loss v1.59 OTOGL Eleanor Williams commented on gene: OTOGL
Monogenic hearing loss v1.59 TSPEAR Emma Ashton reviewed gene: TSPEAR: Rating: AMBER; Mode of pathogenicity: ; Publications: 26969326, 2678063; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 TNC Emma Ashton reviewed gene: TNC: Rating: AMBER; Mode of pathogenicity: ; Publications: 23936043; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 TJP2 Emma Ashton reviewed gene: TJP2: Rating: AMBER; Mode of pathogenicity: ; Publications: 24752540; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 SLC17A8 Emma Ashton reviewed gene: SLC17A8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 RPGR Emma Ashton reviewed gene: RPGR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 MIR96 Emma Ashton reviewed gene: MIR96: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 HGF Emma Ashton reviewed gene: HGF: Rating: AMBER; Mode of pathogenicity: ; Publications: 19576567, 27610647; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 HARS2 Emma Ashton reviewed gene: HARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: 27650058; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 HARS Emma Ashton reviewed gene: HARS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 GJB6 Emma Ashton reviewed gene: GJB6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 DIAPH1 Emma Ashton reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 DIABLO Emma Ashton reviewed gene: DIABLO: Rating: AMBER; Mode of pathogenicity: ; Publications: 21722859, 26969326; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 CRYM Emma Ashton reviewed gene: CRYM: Rating: AMBER; Mode of pathogenicity: ; Publications: 420014; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 CEACAM16 Emma Ashton reviewed gene: CEACAM16: Rating: GREEN; Mode of pathogenicity: ; Publications: 21368133, 25589040, 26648831; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 CCDC50 Emma Ashton reviewed gene: CCDC50: Rating: GREEN; Mode of pathogenicity: ; Publications: 24875298, 27911912, 27068579, 17503326; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 BDP1 Emma Ashton reviewed gene: BDP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 ATP2B2 Emma Ashton reviewed gene: ATP2B2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 DIAPH3 Emma Ashton reviewed gene: DIAPH3: Rating: GREEN; Mode of pathogenicity: ; Publications: 20624953, 27658576; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 NARS2 Emma Ashton reviewed gene: NARS2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 CD164 Emma Ashton reviewed gene: CD164: Rating: RED; Mode of pathogenicity: ; Publications: 26197441; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 KITLG Emma Ashton reviewed gene: KITLG: Rating: AMBER; Mode of pathogenicity: ; Publications: 26522471, 28504826; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 SYNE4 Emma Ashton reviewed gene: SYNE4: Rating: GREEN; Mode of pathogenicity: ; Publications: 24164807, 6824437 ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 SIX5 Emma Ashton reviewed gene: SIX5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 S1PR2 Emma Ashton reviewed gene: S1PR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 26805784, 29776397; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.59 OTOGL Emma Ashton reviewed gene: OTOGL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v1.58 NARS2 Eleanor Williams gene: NARS2 was added
gene: NARS2 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: NARS2 was set to Unknown
Added comment: Added at suggestion of Emma Ashton, GOSH
Sources: Expert list
Monogenic hearing loss v1.57 CD164 Eleanor Williams gene: CD164 was added
gene: CD164 was added to Hearing loss. Sources: Expert list
Mode of inheritance for gene: CD164 was set to Unknown
Added comment: Added at suggestion of Emma Ashton, GOSH
Sources: Expert list
Monogenic hearing loss v1.56 DMXL2 Anna de Burca reviewed gene: DMXL2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30237576; Phenotypes: Polyendocrine-polyneuropathy syndrome, Deafness, autosomal dominant 71; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.56 HTRA2 Anna de Burca reviewed gene: HTRA2: Rating: RED; Mode of pathogenicity: None; Publications: 27208207, 27696117; Phenotypes: Infantile neurodegeneration and 3-methylglutaconic aciduria; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.56 RIPOR2 Anna de Burca reviewed gene: RIPOR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24958875, 27269051, 30280293; Phenotypes: Sensorineural hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v1.56 BCAP31 Eleanor Williams commented on gene: BCAP31
Monogenic hearing loss v1.55 TBC1D24 Louise Daugherty Publications for gene: TBC1D24 were set to 10574461; 10741954; 20727515; 20797691; 21087195; 22211675; 23343562; 23526554; 24291220; 24387994; 24729539; 24729547
Monogenic hearing loss v1.54 TBC1D24 Louise Daugherty Classified gene: TBC1D24 as Green List (high evidence)
Monogenic hearing loss v1.54 TBC1D24 Louise Daugherty Added comment: Comment on list classification: Changed from Red to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Monogenic hearing loss v1.54 TBC1D24 Louise Daugherty Gene: tbc1d24 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.53 TBC1D24 Louise Daugherty Mode of inheritance for gene: TBC1D24 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v1.52 TBC1D24 Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Monogenic hearing loss v1.52 TBC1D24 Louise Daugherty Publications for gene: TBC1D24 were set to
Monogenic hearing loss v1.51 TBC1D24 Louise Daugherty Phenotypes for gene: TBC1D24 were changed from Deafness , autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation to Deafness, autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation
Monogenic hearing loss v1.50 TBC1D24 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes that indicate relevance to inclusion on the Hearing loss panel from OMIM. removed: Myoclonic epilepsy, infantile, familial, 605021;Myoclonicepilepsy,infantile,familial,605021Epilepticencephalopathy,earlyinfantile,16,615338
Monogenic hearing loss v1.50 TBC1D24 Louise Daugherty Phenotypes for gene: TBC1D24 were changed from Myoclonic epilepsy, infantile, familial, 605021; Myoclonicepilepsy,infantile,familial,605021Epilepticencephalopathy,earlyinfantile,16,615338 to Deafness , autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation
Monogenic hearing loss v1.49 Ellen McDonagh List of related panels changed from Congenital hearing impairment;Autosomal dominant deafness;Congenital hearing impairment (profound/severe) to Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe)
Monogenic hearing loss v1.48 Ellen McDonagh Panel name changed from Congenital hearing impairment (profound/severe) to Hearing loss
List of related panels changed from Congenital hearing impairment; Autosomal dominant deafness to Congenital hearing impairment;Autosomal dominant deafness;Congenital hearing impairment (profound/severe)
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Monogenic hearing loss v1.47 KCNQ4 Ellen McDonagh Publications for gene: KCNQ4 were set to 26036578; 10025409; 10080176; 10369879; 10571947; 10760249; 10760300; 10925378; 11450843; 12112653; 12670425; 16596322; 18030493; 20966080; 8035838; 9126484
Monogenic hearing loss v1.46 KCNQ4 Ellen McDonagh commented on gene: KCNQ4: Updating the mode of inheritance from monoallelic to 'both', after feedback from an Expert Reviewer who has another case in their lab. Feedback also included that the mice model with a homozygous 'dominant negative' mutation are also affected by progressive deafness.
Monogenic hearing loss v1.46 KCNQ4 Ellen McDonagh Source Expert was removed from KCNQ4.
Mode of inheritance for gene KCNQ4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Monogenic hearing loss v1.45 KCNQ4 Ellen McDonagh Tag watchlist tag was added to gene: KCNQ4.
Monogenic hearing loss v1.45 KCNQ4 Ellen McDonagh Publications for gene: KCNQ4 were set to 26036578; 10025409; 10080176; 10369879; 10571947; 10760249; 10760300; 10925378; 11450843; 12112653; 12670425; 16596322; 18030493; 20966080; 8035838; 9126484
Monogenic hearing loss v1.44 KCNQ4 Ellen McDonagh Publications for gene: KCNQ4 were set to PMID:10025409; 10080176; 10369879; 10571947; 10760249; 10760300; 10925378; 11450843; 12112653; 12670425; 16596322; 18030493; 20966080; 8035838; 9126484
Monogenic hearing loss v1.43 WHRN Ellen McDonagh commented on gene: WHRN
Monogenic hearing loss v1.43 KARS Ellen McDonagh commented on gene: KARS
Monogenic hearing loss v1.43 ILDR1 Ellen McDonagh commented on gene: ILDR1
Monogenic hearing loss v1.43 HSD17B4 Ellen McDonagh commented on gene: HSD17B4
Monogenic hearing loss v1.43 GRXCR1 Ellen McDonagh commented on gene: GRXCR1
Monogenic hearing loss v1.43 GRHL2 Ellen McDonagh commented on gene: GRHL2: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 GPSM2 Ellen McDonagh commented on gene: GPSM2
Monogenic hearing loss v1.43 GJB2 Ellen McDonagh commented on gene: GJB2: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 GJB2 Ellen McDonagh commented on gene: GJB2: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 GIPC3 Ellen McDonagh commented on gene: GIPC3
Monogenic hearing loss v1.43 EYA4 Ellen McDonagh commented on gene: EYA4: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 EYA1 Ellen McDonagh commented on gene: EYA1
Monogenic hearing loss v1.43 ESRRB Ellen McDonagh commented on gene: ESRRB
Monogenic hearing loss v1.43 EDNRB Ellen McDonagh commented on gene: EDNRB: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 EDN3 Ellen McDonagh commented on gene: EDN3: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 DFNA5 Ellen McDonagh commented on gene: DFNA5: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 DFNB59 Ellen McDonagh commented on gene: DFNB59
Monogenic hearing loss v1.43 COCH Ellen McDonagh commented on gene: COCH: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 CLRN1 Ellen McDonagh commented on gene: CLRN1
Monogenic hearing loss v1.43 CLPP Ellen McDonagh commented on gene: CLPP
Monogenic hearing loss v1.43 CLDN14 Ellen McDonagh commented on gene: CLDN14
Monogenic hearing loss v1.43 CIB2 Ellen McDonagh commented on gene: CIB2
Monogenic hearing loss v1.43 CDH23 Ellen McDonagh commented on gene: CDH23: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss v1.43 FOXI1 Ellen McDonagh commented on gene: FOXI1: A new publication reporting on three families with early-onset sensorineural deafness and distal renal tubular acidosis.
Monogenic hearing loss v1.43 FOXI1 Ellen McDonagh Publications for gene: FOXI1 were set to PMID:12642503; 15173882; 16932748; 17503324; 7957066; 8825632; 9843211
Monogenic hearing loss v1.42 FOXI1 Ellen McDonagh Added comment: Comment on mode of inheritance: See PMID: 29242249
Monogenic hearing loss v1.42 FOXI1 Ellen McDonagh Mode of inheritance for gene: FOXI1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss KCNQ4 Ellen McDonagh edited their review of gene: KCNQ4
Monogenic hearing loss KCNQ4 Ellen McDonagh edited their review of gene: KCNQ4
Monogenic hearing loss SPATA5 Rachel Jones classified SPATA5 as Green List (high evidence)
Monogenic hearing loss SPATA5 Rachel Jones Added gene to panel
Monogenic hearing loss KCNQ4 Ellen McDonagh commented on gene: KCNQ4
Monogenic hearing loss LARS2 Ellen McDonagh commented on gene: LARS2
Monogenic hearing loss LHFPL5 Ellen McDonagh commented on gene: LHFPL5
Monogenic hearing loss LOXHD1 Ellen McDonagh commented on gene: LOXHD1
Monogenic hearing loss LRTOMT Ellen McDonagh commented on gene: LRTOMT
Monogenic hearing loss MARVELD2 Ellen McDonagh commented on gene: MARVELD2
Monogenic hearing loss MSRB3 Ellen McDonagh commented on gene: MSRB3
Monogenic hearing loss MYH14 Ellen McDonagh commented on gene: MYH14
Monogenic hearing loss MYH9 Ellen McDonagh commented on gene: MYH9
Monogenic hearing loss MYO15A Ellen McDonagh commented on gene: MYO15A
Monogenic hearing loss MYO3A Ellen McDonagh commented on gene: MYO3A
Monogenic hearing loss MYO6 Ellen McDonagh commented on gene: MYO6
Monogenic hearing loss MYO7A Ellen McDonagh commented on gene: MYO7A
Monogenic hearing loss OTOF Ellen McDonagh commented on gene: OTOF
Monogenic hearing loss OTOG Ellen McDonagh commented on gene: OTOG
Monogenic hearing loss P2RX2 Ellen McDonagh commented on gene: P2RX2
Monogenic hearing loss PAX3 Ellen McDonagh commented on gene: PAX3
Monogenic hearing loss PCDH15 Ellen McDonagh commented on gene: PCDH15
Monogenic hearing loss POU3F4 Ellen McDonagh commented on gene: POU3F4
Monogenic hearing loss POU4F3 Ellen McDonagh commented on gene: POU4F3
Monogenic hearing loss PRPS1 Ellen McDonagh commented on gene: PRPS1
Monogenic hearing loss RDX Ellen McDonagh commented on gene: RDX
Monogenic hearing loss SERPINB6 Ellen McDonagh commented on gene: SERPINB6
Monogenic hearing loss SIX1 Ellen McDonagh commented on gene: SIX1
Monogenic hearing loss SLC26A4 Ellen McDonagh commented on gene: SLC26A4
Monogenic hearing loss SMPX Ellen McDonagh commented on gene: SMPX
Monogenic hearing loss SOX10 Ellen McDonagh commented on gene: SOX10
Monogenic hearing loss TECTA Ellen McDonagh commented on gene: TECTA
Monogenic hearing loss TMC1 Ellen McDonagh commented on gene: TMC1
Monogenic hearing loss TMIE Ellen McDonagh commented on gene: TMIE
Monogenic hearing loss TMPRSS3 Ellen McDonagh commented on gene: TMPRSS3
Monogenic hearing loss TPRN Ellen McDonagh commented on gene: TPRN
Monogenic hearing loss TRIOBP Ellen McDonagh commented on gene: TRIOBP
Monogenic hearing loss USH1C Ellen McDonagh commented on gene: USH1C
Monogenic hearing loss USH1G Ellen McDonagh commented on gene: USH1G
Monogenic hearing loss USH2A Ellen McDonagh commented on gene: USH2A
Monogenic hearing loss WFS1 Ellen McDonagh commented on gene: WFS1
Monogenic hearing loss STRC Ellen McDonagh commented on gene: STRC
Monogenic hearing loss OTOA Ellen McDonagh commented on gene: OTOA
Monogenic hearing loss STRC Lampros Mavrogiannis reviewed STRC
Monogenic hearing loss OTOA Lampros Mavrogiannis reviewed OTOA
Monogenic hearing loss WFS1 Lampros Mavrogiannis reviewed WFS1
Monogenic hearing loss USH2A Lampros Mavrogiannis reviewed USH2A
Monogenic hearing loss USH1G Lampros Mavrogiannis reviewed USH1G
Monogenic hearing loss USH1C Lampros Mavrogiannis reviewed USH1C
Monogenic hearing loss TRIOBP Lampros Mavrogiannis reviewed TRIOBP
Monogenic hearing loss TPRN Lampros Mavrogiannis reviewed TPRN
Monogenic hearing loss TMPRSS3 Lampros Mavrogiannis reviewed TMPRSS3
Monogenic hearing loss TMIE Lampros Mavrogiannis reviewed TMIE
Monogenic hearing loss TMC1 Lampros Mavrogiannis reviewed TMC1
Monogenic hearing loss TECTA Lampros Mavrogiannis reviewed TECTA
Monogenic hearing loss SOX10 Lampros Mavrogiannis reviewed SOX10
Monogenic hearing loss SMPX Lampros Mavrogiannis reviewed SMPX
Monogenic hearing loss SLC26A4 Lampros Mavrogiannis reviewed SLC26A4
Monogenic hearing loss SIX1 Lampros Mavrogiannis reviewed SIX1
Monogenic hearing loss SERPINB6 Lampros Mavrogiannis reviewed SERPINB6
Monogenic hearing loss RDX Lampros Mavrogiannis reviewed RDX
Monogenic hearing loss PRPS1 Lampros Mavrogiannis reviewed PRPS1
Monogenic hearing loss POU4F3 Lampros Mavrogiannis reviewed POU4F3
Monogenic hearing loss POU3F4 Lampros Mavrogiannis reviewed POU3F4
Monogenic hearing loss PCDH15 Lampros Mavrogiannis reviewed PCDH15
Monogenic hearing loss PAX3 Lampros Mavrogiannis reviewed PAX3
Monogenic hearing loss P2RX2 Lampros Mavrogiannis reviewed P2RX2
Monogenic hearing loss OTOG Lampros Mavrogiannis reviewed OTOG
Monogenic hearing loss OTOF Lampros Mavrogiannis reviewed OTOF
Monogenic hearing loss MYO7A Lampros Mavrogiannis reviewed MYO7A
Monogenic hearing loss MYO6 Lampros Mavrogiannis reviewed MYO6
Monogenic hearing loss MYO3A Lampros Mavrogiannis reviewed MYO3A
Monogenic hearing loss MYO15A Lampros Mavrogiannis reviewed MYO15A
Monogenic hearing loss MYH9 Lampros Mavrogiannis reviewed MYH9
Monogenic hearing loss MYH14 Lampros Mavrogiannis reviewed MYH14
Monogenic hearing loss MSRB3 Lampros Mavrogiannis reviewed MSRB3
Monogenic hearing loss MITF Lampros Mavrogiannis reviewed MITF
Monogenic hearing loss MARVELD2 Lampros Mavrogiannis reviewed MARVELD2
Monogenic hearing loss LRTOMT Lampros Mavrogiannis reviewed LRTOMT
Monogenic hearing loss LOXHD1 Lampros Mavrogiannis reviewed LOXHD1
Monogenic hearing loss LHFPL5 Lampros Mavrogiannis reviewed LHFPL5
Monogenic hearing loss LARS2 Lampros Mavrogiannis reviewed LARS2
Monogenic hearing loss KCNQ4 Lampros Mavrogiannis reviewed KCNQ4
Monogenic hearing loss KCNQ1 Lampros Mavrogiannis reviewed KCNQ1
Monogenic hearing loss KCNE1 Lampros Mavrogiannis reviewed KCNE1
Monogenic hearing loss KARS Lampros Mavrogiannis reviewed KARS
Monogenic hearing loss ILDR1 Lampros Mavrogiannis reviewed ILDR1
Monogenic hearing loss HSD17B4 Lampros Mavrogiannis reviewed HSD17B4
Monogenic hearing loss GRXCR1 Lampros Mavrogiannis reviewed GRXCR1
Monogenic hearing loss GRHL2 Lampros Mavrogiannis reviewed GRHL2
Monogenic hearing loss GPSM2 Lampros Mavrogiannis reviewed GPSM2
Monogenic hearing loss GJB2 Lampros Mavrogiannis reviewed GJB2
Monogenic hearing loss GIPC3 Lampros Mavrogiannis reviewed GIPC3
Monogenic hearing loss EYA4 Lampros Mavrogiannis reviewed EYA4
Monogenic hearing loss EYA1 Lampros Mavrogiannis reviewed EYA1
Monogenic hearing loss ESRRB Lampros Mavrogiannis reviewed ESRRB
Monogenic hearing loss EDNRB Lampros Mavrogiannis reviewed EDNRB
Monogenic hearing loss EDN3 Lampros Mavrogiannis reviewed EDN3
Monogenic hearing loss DFNB59 Lampros Mavrogiannis reviewed DFNB59
Monogenic hearing loss DFNA5 Lampros Mavrogiannis reviewed DFNA5
Monogenic hearing loss COCH Lampros Mavrogiannis reviewed COCH
Monogenic hearing loss CLRN1 Lampros Mavrogiannis reviewed CLRN1
Monogenic hearing loss CLPP Lampros Mavrogiannis reviewed CLPP
Monogenic hearing loss CLDN14 Lampros Mavrogiannis reviewed CLDN14
Monogenic hearing loss CIB2 Lampros Mavrogiannis reviewed CIB2
Monogenic hearing loss CDH23 Lampros Mavrogiannis reviewed CDH23
Monogenic hearing loss ACTG1 Lampros Mavrogiannis reviewed ACTG1
Monogenic hearing loss WHRN Lampros Mavrogiannis reviewed WHRN
Monogenic hearing loss FGFR1 Ellen McDonagh commented on FGFR1
Monogenic hearing loss SERAC1 Louise Daugherty classified SERAC1 as Green List (high evidence)
Monogenic hearing loss SERAC1 Louise Daugherty reviewed SERAC1
Monogenic hearing loss SGPL1 Sarah Leigh classified SGPL1 as green
Monogenic hearing loss SGPL1 Sarah Leigh added SGPL1 to panel
Monogenic hearing loss SGPL1 Sarah Leigh reviewed SGPL1
Monogenic hearing loss FAM65B Louise Daugherty commented on FAM65B
Monogenic hearing loss HAAO Ellen McDonagh classified HAAO as green
Monogenic hearing loss HTRA2 Sarah Leigh classified HTRA2 as amber
Monogenic hearing loss HTRA2 Sarah Leigh classified HTRA2 as amber
Monogenic hearing loss HTRA2 Sarah Leigh commented on HTRA2
Monogenic hearing loss HTRA2 Sarah Leigh added HTRA2 to panel
Monogenic hearing loss HTRA2 Sarah Leigh reviewed HTRA2
Monogenic hearing loss DFNA5 Louise Daugherty commented on DFNA5
Monogenic hearing loss ERAL1 Sarah Leigh added ERAL1 to panel
Monogenic hearing loss ERAL1 Sarah Leigh reviewed ERAL1
Monogenic hearing loss DACT1 Louise Daugherty added DACT1 to panel
Monogenic hearing loss DACT1 Louise Daugherty reviewed DACT1
Monogenic hearing loss HAAO Ellen McDonagh classified HAAO as amber
Monogenic hearing loss HAAO Ellen McDonagh edited their review of HAAO
Monogenic hearing loss HAAO Ellen McDonagh added HAAO to panel
Monogenic hearing loss HAAO Ellen McDonagh reviewed HAAO
Monogenic hearing loss FAM65B Ellen McDonagh classified FAM65B as amber
Monogenic hearing loss FAM65B Ellen McDonagh classified FAM65B as amber
Monogenic hearing loss FAM65B Ellen McDonagh commented on FAM65B
Monogenic hearing loss DMXL2 Ellen McDonagh classified DMXL2 as amber
Monogenic hearing loss DMXL2 Ellen McDonagh added DMXL2 to panel
Monogenic hearing loss DMXL2 Ellen McDonagh reviewed DMXL2
Monogenic hearing loss CEP78 Ellen McDonagh classified CEP78 as green
Monogenic hearing loss CEP78 Ellen McDonagh added CEP78 to panel
Monogenic hearing loss CEP78 Ellen McDonagh reviewed CEP78
Monogenic hearing loss DFNB59 Louise Daugherty commented on DFNB59
Monogenic hearing loss MT-RNR1 Ellen McDonagh commented on MT-RNR1
Monogenic hearing loss MIR96 Ellen McDonagh commented on MIR96
Monogenic hearing loss MIR183 Ellen McDonagh commented on MIR183
Monogenic hearing loss GJA1P1 Ellen McDonagh commented on GJA1P1
Monogenic hearing loss DFNB31 Louise Daugherty commented on DFNB31
Monogenic hearing loss LARGE Louise Daugherty commented on LARGE