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Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Ian Berry, there are now five unrelated families with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Ian Berry, there are now at least nine probands with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.94 CADM3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Ian Berry, there are now five unrelated families with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update as the scope of this panel has now been expanded to include complex cases of neuropathy.
Biallelic variants in the GAN gene cause giant axonal neuropathy. This childhood onset polyneuropathy results in progressive neurodegeneration of both the peripheral and central nervous systems. More than 10 unrelated cases have been reported in the literature which is sufficient for making this gene Green (PMIDs: 18595793; 19231187; 20949505; 27852232; 36866531)
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain, and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram changed review comment from: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature; to: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Hereditary neuropathy or pain disorder v3.89 RTN2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of RTN2 biallelic variants with distal hereditary motor neuropathy. Hence, this gene should be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.88 RTN2 Achchuthan Shanmugasundram gene: RTN2 was added
gene: RTN2 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: RTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTN2 were set to 38527963
Phenotypes for gene: RTN2 were set to distal hereditary motor neuropathy, MONDO:0018894
Review for gene: RTN2 was set to GREEN
Added comment: PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy.

All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.
Sources: Literature
Hereditary neuropathy or pain disorder v3.87 PDXK Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v3.86 PDXK Achchuthan Shanmugasundram gene: PDXK was added
gene: PDXK was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503; 32522499
Phenotypes for gene: PDXK were set to Neuropathy, hereditary motor and sensory, type VIC, with optic atrophy, OMIM:618511
Review for gene: PDXK was set to GREEN
Added comment: PMID:31187503 - Five individuals from two unrelated families were reported with biallelic PDXK variants and with primary axonal polyneuropathy and optic atrophy. This association was also supported by results from cell-based functional assays. The biochemical profile can be rescued with PLP supplementation associated with clinical improvement.

PMID:32522499 - Two affected siblings with a novel biallelic missense PDXK variant were reported with a similar phenotype as reported in PMID:31187503 with earlier onset. Functional analysis showed that this variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels.

This gene has been associated with relevant phenotypes in OMIM (MIM #618511), but not yet in Gene2Phenotype.
Sources: Literature
Hereditary neuropathy or pain disorder v3.84 SPG7 Sarah Leigh changed review comment from: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Williams Kirsty), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).; to: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Kirsty Williams), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).
Hereditary neuropathy or pain disorder v3.83 SPG7 Sarah Leigh edited their review of gene: SPG7: Added comment: SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive (OMIM:607259) and have a definitive association with the same condition on the Eye panel at Gen2Phen. Various phenotypic features are apparent in cases of OMIM:607259. Peripheral neuropathy has been reported in at least three cases (PMID: 35096021, in the review on this panel by Williams Kirsty), and optical neuropathy has been reported in many more cases (as mentioned in PMID:35243150).; Changed rating: GREEN; Changed publications to: 30098094, 35637455, 35096021, 35243150, 22964162
Hereditary neuropathy or pain disorder v3.83 XK Alexander Rossor commented on gene: XK: Should be included in R78 as now inlcudes many other complex phenotype genes that can present with neuropathy
Hereditary neuropathy or pain disorder v3.83 TYMP Alexander Rossor edited their review of gene: TYMP: Added comment: Can present with neuropathy and should be included in R78 panel; Changed publications to: 21933806
Hereditary neuropathy or pain disorder v3.83 SURF1 Alexander Rossor edited their review of gene: SURF1: Added comment: Should be included as R78 now includes complex phenotype genes; Changed publications to: 27475922, 12026244, 24027061
Hereditary neuropathy or pain disorder v3.83 SPTBN4 Alexander Rossor commented on gene: SPTBN4
Hereditary neuropathy or pain disorder v3.83 SLC25A19 Alexander Rossor edited their review of gene: SLC25A19: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Acute encephalopathic episodes and paralysis following febrile illness with almost complete recovery. Absent sensory-motor action potential during illness. Bilateral striatal necrosis on MRI. Additional chronic progressive axonal neuropathy
Hereditary neuropathy or pain disorder v3.83 SCARB2 Alexander Rossor edited their review of gene: SCARB2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 21670406, 19597094
Hereditary neuropathy or pain disorder v3.83 SACS Alexander Rossor edited their review of gene: SACS: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 30460542
Hereditary neuropathy or pain disorder v3.83 POLR3A Alexander Rossor commented on gene: POLR3A: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 PNPLA6 Alexander Rossor commented on gene: PNPLA6: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 PMM2 Alexander Rossor edited their review of gene: PMM2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Neonatal onset, leukodystrophy, abnormal serum glycoproteins, mental retardation, hypotonia, ataxia, retinitis pigmentosa, seizures, slowly progressive neuropathy with SNCV, severe infections, hepatic insufficiency and cardiomyopathy.
Hereditary neuropathy or pain disorder v3.83 PLP1 Alexander Rossor edited their review of gene: PLP1: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 12601703
Hereditary neuropathy or pain disorder v3.83 PEX7 Alexander Rossor edited their review of gene: PEX7: Added comment: Should be included in R78 as can present with neuropathy and other complex disease are now include in R78; Changed publications to: 11493716
Hereditary neuropathy or pain disorder v3.83 PEX10 Alexander Rossor edited their review of gene: PEX10: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 27230853, 20695019
Hereditary neuropathy or pain disorder v3.83 PDYN Alexander Rossor commented on gene: PDYN: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 NAGA Alexander Rossor commented on gene: NAGA: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 MTTP Alexander Rossor commented on gene: MTTP: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 MMACHC Alexander Rossor edited their review of gene: MMACHC: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed phenotypes to: Onset infancy to adulthood, thrombotic thrombocytopenia with encephalopathy, myelopathy, renal and pulmonary complications (can be life threatening), retinitis pigmentosa, axonal motor neuropathy. Treated with high dose vitamin B12.
Hereditary neuropathy or pain disorder v3.83 LYST Alexander Rossor commented on gene: LYST: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 IARS2 Alexander Rossor edited their review of gene: IARS2: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 25130867, 28328135, 30041933, 30419932
Hereditary neuropathy or pain disorder v3.83 GBA2 Alexander Rossor commented on gene: GBA2: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 BCKDHB Alexander Rossor edited their review of gene: BCKDHB: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 18855118, 11180212; Changed phenotypes to: Maple Syrup Urine Disease, Metabolic encephalopathy, elevated branched chain amino acids in urine, acute axonal neuropathy
Hereditary neuropathy or pain disorder v3.83 B4GALNT1 Alexander Rossor commented on gene: B4GALNT1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 APOA1 Alexander Rossor commented on gene: APOA1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 AP1S1 Alexander Rossor Deleted their comment
Hereditary neuropathy or pain disorder v3.83 AP1S1 Alexander Rossor commented on gene: AP1S1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 AGXT Alexander Rossor edited their review of gene: AGXT: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 4701948, 25363903
Hereditary neuropathy or pain disorder v3.83 AGTPBP1 Alexander Rossor commented on gene: AGTPBP1: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 ABHD12 Alexander Rossor edited their review of gene: ABHD12: Added comment: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46; Changed publications to: 29571850, 20797687
Hereditary neuropathy or pain disorder v3.83 GAN Alexander Rossor commented on gene: GAN: should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46
Hereditary neuropathy or pain disorder v3.83 FXN Alexander Rossor edited their review of gene: FXN: Added comment: FA can present with a sensory neuropathy and should be included in the R78 panel. A missense may prompt testing for an expansion in the other allele.; Changed publications to: 20339857
Hereditary neuropathy or pain disorder v3.83 GALC Alexander Rossor edited their review of gene: GALC: Added comment: Can present with peripheral neuropathy and should be included in R78 panel; Changed publications to: 26840509; Changed phenotypes to: Krabbe. Spastic paraplegia, developmental delay, optic atrophy, adult onset has spastic paraplegia and sensory-motor axonal neuropathy with slow or normal conduction velocities, MRI shows leukodystrophy
Hereditary neuropathy or pain disorder v3.82 HMBS Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence available (three unrelated families) for the association of biallelic HMBS variants with peripheral neuropathy. Hence, the MOI should be updated from 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS review.
Hereditary neuropathy or pain disorder v3.79 COQ7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases) for the promotion of this gene to green rating in the next GMS review.
Hereditary neuropathy or pain disorder v3.76 COQ7 Achchuthan Shanmugasundram changed review comment from: PMID:36454683 reported three siblings of Portuguese decent with distal hereditary motor neuropathy and identified with a homozygous COQ7 variant that disrupted the start codon of the main COQ7 isoform 1 (c.3G-T).

PMID:36758993 reported two unrelated males of Chinese decent, who developed slowly progressive distal muscle weakness and atrophy at 14 to 15 years of age. They were identified with compound heterozygous variants in COQ7 gene (family 1: c.253-2A-T/ p.Leu156Gln & c.467T-A/ p.Leu156Gln; family 2: c.160C-T/ p.Arg54Trp & c.467T-G/ p.Leu156Arg).

PMID:3707755 reported three siblings of Syrian decent who presented with progressive distal limb muscle weakness and atrophy due to a length-dependent peripheral motor neuropathy. They were identified with a homozygous COQ7 variant (c.1A-G).

This gene has been associated with relevant phenotype in OMIM (MIM #620402), but not in Gene2Phenotype.; to: PMID:36454683 reported three siblings of Portuguese decent with distal hereditary motor neuropathy and identified with a homozygous COQ7 variant that disrupted the start codon of the main COQ7 isoform 1 (c.3G-T).

PMID:36758993 reported two unrelated males of Chinese decent, who developed slowly progressive distal muscle weakness and atrophy at 14 to 15 years of age. They were identified with compound heterozygous variants in COQ7 gene (family 1: c.253-2A-T/ p.Leu156Gln & c.467T-A/ p.Leu156Gln; family 2: c.160C-T/ p.Arg54Trp & c.467T-G/ p.Leu156Arg).

PMID:37077559 reported three siblings of Syrian decent who presented with progressive distal limb muscle weakness and atrophy due to a length-dependent peripheral motor neuropathy. They were identified with a homozygous COQ7 variant (c.1A-G).

This gene has been associated with relevant phenotype in OMIM (MIM #620402), but not in Gene2Phenotype.
Hereditary neuropathy or pain disorder v3.74 COQ7 Lucy Jackson gene: COQ7 was added
gene: COQ7 was added to Hereditary neuropathy or pain disorder. Sources: NHS GMS
Mode of inheritance for gene: COQ7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ7 were set to PMID: 36758993; 37077559
Phenotypes for gene: COQ7 were set to autosomal recessive distal hereditary motor neuronopathy-9 (HMNR9)
Review for gene: COQ7 was set to GREEN
Added comment: This gene is associated with autosomal recessive distal hereditary motor neuronopathy-9 (HMNR9)
Sources: NHS GMS
Hereditary neuropathy or pain disorder v3.74 PDK3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v3.74 PCYT2 Achchuthan Shanmugasundram changed review comment from: PMID:35243002 reported two brothers with a novel homozygous missense variant in the first catalytic domain of PCYT2 (c.88T>G/ p.Cys30Gly). Although these two patients shared several phenotypic features with previously reported patients with syndromic spastic paraplegia including short stature, spastic tetraparesis, cerebellar ataxia, epilepsy, and cognitive decline, these were the first patients reported with axonal polyneuropathy.; to: PMID:35243002 reported two brothers with a novel homozygous missense variant in the first catalytic domain of PCYT2 (c.88T>G/ p.Cys30Gly). Although these two patients shared several phenotypic features with previously reported patients with syndromic spastic paraplegia including short stature, spastic tetraparesis, cerebellar ataxia, epilepsy, and cognitive decline, axonal polyneuropathy reported in these two brothers were not reported in any previous cases.
Hereditary neuropathy or pain disorder v3.71 EMILIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are two unrelated families in support of the association of monoallelic EMILIN1 variants with peripheral neuropathy and hence this gene should be rated amber with current evidence.
Hereditary neuropathy or pain disorder v3.68 SLC12A6 Arina Puzriakova commented on gene: SLC12A6
Hereditary neuropathy or pain disorder v3.66 PSMC3 Achchuthan Shanmugasundram gene: PSMC3 was added
gene: PSMC3 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC3 were set to 32500975
Phenotypes for gene: PSMC3 were set to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354
Review for gene: PSMC3 was set to AMBER
Added comment: 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.
Sources: Literature
Hereditary neuropathy or pain disorder v3.65 SARS Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of SARS1 gene in this panel in the next GMS review.
Hereditary neuropathy or pain disorder v3.62 SARS Achchuthan Shanmugasundram commented on gene: SARS: Added new-gene-name tag, new approved HGNC gene symbol for SARS is SARS1.
Hereditary neuropathy or pain disorder v3.62 SARS Achchuthan Shanmugasundram changed review comment from: PMID:36088542 - Two different heterozygous missense variants within the aminoacylation domain of SARS1 gene was identified in 16 affected individuals from three unrelated families with Charcot-Marie-Tooth (CMT) disease. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation.

PMID:37706277 - A female patient with demyelinating CMT was identified with a heterozygous variant in SARS1 gene.


Biallelic variants in this gene have already been associated with relevant phenotypes in both OMIM (MIM #617709) and Gene2Phenotype, while monoallelic variants are associated with phenotype only in Gene2Phenotype (with 'limited' rating in the DD panel).; to: PMID:36088542 - Two different heterozygous missense variants within the aminoacylation domain of SARS1 gene was identified in 16 affected individuals from three unrelated families with Charcot-Marie-Tooth (CMT) disease. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation.

PMID:37706277 - A female patient with demyelinating CMT was identified with a heterozygous variant in SARS1 gene.

Biallelic variants in this gene have already been associated with relevant phenotypes in both OMIM (MIM #617709) and Gene2Phenotype, while monoallelic variants are associated with phenotype only in Gene2Phenotype (with 'limited' rating in the DD panel).
Hereditary neuropathy or pain disorder v3.62 SARS Christopher Record gene: SARS was added
gene: SARS was added to Hereditary neuropathy or pain disorder. Sources: Expert Review
Mode of inheritance for gene: SARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SARS were set to 37706277,36088542
Phenotypes for gene: SARS were set to CMTi
Penetrance for gene: SARS were set to Complete
Review for gene: SARS was set to GREEN
Added comment: Dominant or de novo dominant plausibly causing CMT in four unrelated families. Another amino-acyl tRNA synthetase causing CMT
Sources: Expert Review
Hereditary neuropathy or pain disorder v3.60 MT-ND6 Dmitrijs Rots gene: MT-ND6 was added
gene: MT-ND6 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
Publications for gene: MT-ND6 were set to PMID: 20301353
Phenotypes for gene: MT-ND6 were set to LHON; peripheral neuropathy
Penetrance for gene: MT-ND6 were set to unknown
Mode of pathogenicity for gene: MT-ND6 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MT-ND6 was set to GREEN
Added comment: Gene is associated with LHON, but GeneReviews states: "Neurologic abnormalities such as postural tremor, peripheral neuropathy, nonspecific myopathy, and movement disorders have been reported to be more common in individuals with LHON than in the general population. ".
Identified in our lab in a young patient with peripheral neuropathy phenotype only.
Sources: Literature
Hereditary neuropathy or pain disorder v3.60 DRP2 Eleanor Williams commented on gene: DRP2
Hereditary neuropathy or pain disorder v3.56 SYT2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene to this panel (six unrelated cases and functional studies) and this gene should therefore be promoted to green rating in the next GMS review.
Hereditary neuropathy or pain disorder v3.52 DHTKD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.
Hereditary neuropathy or pain disorder v3.48 SPTAN1 Sarah Leigh Added comment: Comment on mode of inheritance: Three unrelated cases have been reported with biallelic SPTAN1 variants (PMID: 31515523 & 34526651) . Neuropathy or pain was not part of the complex phenotypes that was seen in these cases.
Hereditary neuropathy or pain disorder v3.47 SPTAN1 Sarah Leigh edited their review of gene: SPTAN1: Added comment: SPTAN1 variants have been associated with Developmental and epileptic encephalopathy 5 (OMIM:613477) and as definitive Gen2Phen gene for the same condition.; Changed rating: GREEN
Hereditary neuropathy or pain disorder v3.47 SPTAN1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.45 AGTPBP1 Achchuthan Shanmugasundram changed review comment from: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Five unrelated patients had (axonal) motor neuropathy.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).; to: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Five unrelated patients had (axonal) motor neuropathy. In addition, functional studies with mouse models have recapitulated the human phenotype.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Hereditary neuropathy or pain disorder v3.45 AGTPBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating at the next major review.
Hereditary neuropathy or pain disorder v3.44 DHX9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases) for promoting this gene to green rating in the next major update.
Hereditary neuropathy or pain disorder v3.40 DNAJC3 Achchuthan Shanmugasundram changed review comment from: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

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 sensorimotor demyelinating and axonal polyneuropathy.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy among several other clinical manifestations.; to: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

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 sensorimotor demyelinating and axonal polyneuropathy.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy.
Hereditary neuropathy or pain disorder v3.40 DNAJC3 Achchuthan Shanmugasundram changed review comment from: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

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 sensorimotor demyelinating and axonal polyneuropathy among several clinical manifestations.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy among several other clinical manifestations.; to: PMID:25466870 - Five individuals from two different families with demyelinating sensorimotor peripheral neuropathy and identified with homozygous DNAJC3 variants (family 1: c.580C>T (p.Arg194Ter); family 2: 72kb del (exons 6-12)).

PMID:28940199 - Cousin of family 1 from PMID:2546687 with the same variant and presented with demyelinating sensorimotor peripheral neuropathy.

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 sensorimotor demyelinating and axonal polyneuropathy.

PMID:33486469 - Two unrelated patients identified with compound heterozygous (patient 1: p.Met1Val & p.Arg346Ter) or homozygous (p.Arg393Ter) variants, of which patient 1 had demyelinating peripheral sensorimotor neuropathy.

PMID:34654017 - One of two siblings identified with homozygous DNAJC3 variant (c.367_1370delAGAA; p.Lys456SerfsTer85) presented with demyelinating neuropathy among several other clinical manifestations.
Hereditary neuropathy or pain disorder v3.39 DNAJC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with DNAJC3 biallelic variants and presenting with demyelinating sensorimotor peripheral neuropathy. Hence, this gene can be promoted to Green at the next GMS review.
Hereditary neuropathy or pain disorder v3.36 PPOX Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Comment on mode of inheritance: There are at least three cases of variegate porphyria reported with biallelic variants in PPOX gene and sensory neuropathy. Hence, the MOI should be updated from "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review.
Hereditary neuropathy or pain disorder v3.35 ITPR3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.31 NTRK1 Achchuthan Shanmugasundram changed review comment from: I agree with Zornitza Stark that it is a complex phenotype. However, neuropathy has been associated with the phenotype in sufficient number of cases and been reviewed by several expert reviewers. Hence, the rating should remain as Green.

This gene has been associated with relevant phenotypes in both OMIM (MIM #256800) and Gene2Phenotype (with 'definitive' rating in DD and skin panels.; to: I agree with Zornitza Stark that it is a complex phenotype. However, neuropathy has been associated with the phenotype in sufficient number of cases and been reviewed by several expert reviewers. Hence, the rating should remain as Green.

This gene has been associated with relevant phenotypes in both OMIM (MIM #256800) and Gene2Phenotype (with 'definitive' rating in DD and skin panels).
Hereditary neuropathy or pain disorder v3.30 MYH14 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four families reported with the same variant (p.Arg941Leu) and with supporting functional studies characterising this variant. As the reported cases came from both Korean and North American families, it is not likely to be a founder variant. Hence, this gene can be promoted to GREEN rating at the next GMS update.
Hereditary neuropathy or pain disorder v3.21 UBA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least nine unrelated cases and supportive functional evidence) available for this gene to be promoted to GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.18 UBA1 Achchuthan Shanmugasundram changed review comment from: As reported in PMID:18179898 and reviewed in OMIM, X-linked spinal muscular atrophy-2 (SMAX2) is characterised by neonatal onset of severe hypotonia, areflexia, and multiple congenital contractures, known as arthrogryposis, associated with loss of anterior horn cells and infantile death. Variants in UBA1 gene ( p.Asn577Asn in three families, and p.Met539Ile and p.Ser547Gly in one family each) were identified in five of screened X-linked spinal muscular atrophy families.

Additional unrelated cases with variants in UBA1 gene are reported in PMIDs: 23518311, 26028276, 31932168 & 32181232.

This gene has been reported with relevant phenotypes in OMIM (MIM #301830).; to: As reported in PMID:18179898 and reviewed in OMIM, X-linked spinal muscular atrophy-2 (SMAX2) is characterised by neonatal onset of severe hypotonia, areflexia, and multiple congenital contractures, known as arthrogryposis, associated with loss of anterior horn cells and infantile death. Variants in UBA1 gene ( p.Asn577Asn in three families, and p.Met539Ile and p.Ser547Gly in one family each) were identified in five of screened X-linked spinal muscular atrophy families.

Additional unrelated cases with variants in UBA1 gene are reported in PMIDs: 23518311, 26028276, 31932168 & 32181232.

This gene has been reported with relevant phenotypes in OMIM (MIM #301830).
Hereditary neuropathy or pain disorder v3.18 VAPB Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases & functional studies from mouse models) for this gene to be promoted to GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.15 DRP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is sufficient evidence (3 unrelated cases and functional studies) for this gene to be promoted to GREEN at the next major review.
Hereditary neuropathy or pain disorder v3.12 GBF1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics) and Dmitrijs Rots (RadboudUMC), this gene should be promoted to GREEN at the next major review as there are four unrelated families identified with monoallelic (2 de novo and 2 dominant) variants in GBF1 gene and reported with distal hereditary motor neuropathies (HMNs)/ axonal Charcot-Marie-Tooth neuropathy (CMT2).
Hereditary neuropathy or pain disorder v3.11 GBF1 Achchuthan Shanmugasundram commented on gene: GBF1: GBF1 is associated with relevant phenotype (MIM #606483) in OMIM, but not in Gene2Phenotype.
Hereditary neuropathy or pain disorder v3.9 SPG7 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal; to: Associated with OMIM:607259 and as definitive Gen2Phen gene for the same condition. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.9 SPG7 Sarah Leigh commented on gene: SPG7
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.; to: As reviewed by Ian Berry (Leeds Genetics Laboratory), there are now three unrelated families reported in literature with Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) and identified with homozygous variant in TDP1 gene. However, all three families are of Arab descent (one family from Saudi Arabia and two families from Oman) and they presented with the same homozygous variant (p.His493Arg).

There are a number of functional studies characterising the function of H493R variant in vitro (PMIDs:15920477, 17948061 & 31723605).

This gene has been associated with phenotypes in OMIM (MIM #607250), but not in Gene2Phenotype.
Hereditary neuropathy or pain disorder v3.6 TDP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can now be promoted to AMBER as there are three unrelated cases. The "founder-effect" tag has been added as they are all of Middle Eastern descent and harboured the same homozygous variant. Hence, it cannot be promoted to green rating.
Hereditary neuropathy or pain disorder v2.25 SCO2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are four unrelated cases identified with CMT type 4 (axonal polyneuropathy).
Hereditary neuropathy or pain disorder v2.22 SCO2 Achchuthan Shanmugasundram Deleted their comment
Hereditary neuropathy or pain disorder v2.22 SCO2 Achchuthan Shanmugasundram commented on gene: SCO2: As reviewed by Zornitza Stark, PMID:29351582 reported two unrelated cases with compound heterozygous variants in SCO2 gene (p.Glu140Lys/ p.Pro169Thr and p.Asp135Gly/ p.Arg171Gln). These two patients presented with axonal polyneuropathy (Charcot-Marie-Tooth disease type 4). They developed predominantly motor neuropathy, survived infancy, and have not yet developed the cardiomyopathy that causes death in early infancy in previously reported patients associated with Mitochondrial complex IV deficiency, nuclear type 2 (MIM #604377).

PMID:31844624 reported two siblings with homozygous missense variant in SCO2 gene (p.Arg255Trp) who presented with cerebellar ataxia, progressive peripheral axonal neuropathy and long survival. Similarly, homozygous variant p.Gly121Arg was identified in two brothers in PMID:35112411 and they were reported with axonal motor neuropathy like the other cases.

Autosomal recessive variants in this gene have been associated with Mitochondrial complex IV deficiency, nuclear type 2 (MIM #604377) in OMIM and Gene2Phenotype, which primarily has a cardiac phenotype. The axonal neuropathy phenotype without cardiac presentation has not yet been recorded in these resources.
Hereditary neuropathy or pain disorder v2.18 TFG Eleanor Williams commented on gene: TFG
Hereditary neuropathy or pain disorder v2.18 SH3TC2 Eleanor Williams commented on gene: SH3TC2
Hereditary neuropathy or pain disorder v2.18 KIF1A Eleanor Williams commented on gene: KIF1A
Hereditary neuropathy or pain disorder v2.18 FIG4 Eleanor Williams commented on gene: FIG4
Hereditary neuropathy or pain disorder v2.18 CPOX Eleanor Williams commented on gene: CPOX
Hereditary neuropathy or pain disorder v2.9 TECPR2 Mafalda Gomes changed review comment from: Neuser et al. (2021) report 17 unrelated cases with a biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss?of?function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.; to: Neuser et al. (2021) report 17 unrelated cases with a biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss of function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.
Hereditary neuropathy or pain disorder v2.7 MYH14 Dmitrijs Rots reviewed gene: MYH14: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 31231018; Phenotypes: Neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v2.3 CADM3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). To date only one paper reports three families with the same missense variant in CADM3. A separate report and/or another variant causing disease would help corroborate this association and so rating Amber for now with a 'watchlist' tag.
Hereditary neuropathy or pain disorder v1.105 FAM126A Eleanor Williams commented on gene: FAM126A
Hereditary neuropathy or pain disorder v1.103 SLC5A6 Sarah Leigh edited their review of gene: SLC5A6: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least 6 variants have been reported in at least 4 unrelated cases. Supportive functional studies and targeted therapeutic interventionyielded clinical improvement in four of the five patients (PMID: 35013551).; Changed rating: GREEN; Changed publications to: 35013551; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v1.103 SLC5A6 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary neuropathy or pain disorder v1.101 TAZ Arina Puzriakova commented on gene: TAZ
Hereditary neuropathy or pain disorder v1.101 MARS Arina Puzriakova commented on gene: MARS
Hereditary neuropathy or pain disorder v1.101 C1orf194 Eleanor Williams commented on gene: C1orf194
Hereditary neuropathy or pain disorder v1.100 SETX Sarah Leigh Added comment: Comment on phenotypes: SETX variants are also associated with Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433, but this condition is not relevant to this narrow panel.
Hereditary neuropathy or pain disorder v1.99 SETX Sarah Leigh Added comment: Comment on publications: PMID: 25025039 - a likely pathogenic variant in SETX reported in a sporadic case with CMT2 and spasticity. Found with a REEP1 variant, and the authors assume digenic pathogenicity.;PMID:25802885 - Identifiy one previously reported variant and three novel variants in 4 families. Report the variants found in CMT patients are likely nonpathogenic due to bioinformatics analysis. Report SETX c.7640T>C is a nonpathogenic rare variant
Hereditary neuropathy or pain disorder v1.97 OPA1 Arina Puzriakova Added comment: Comment on list classification: It has now been agreed that all genes causing neuropathy as a key feature of a phenotype, even if in the context of other syndromic symptoms, should be included on this panel to minimise the risk of missing cases. For this reason it would now be appropriate to rate this gene as Green on R78.
Hereditary neuropathy or pain disorder v1.96 OPA1 Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from 'monoallelic' only to 'both mono- and biallelic'. Biallelic variants cause Behr syndrome (MIM# 210000) which is also associated with axonal sensorimotor peripheral neuropathy (PMID: 20157015; 25012220; 25146916). Sufficient cases have been reported to rate as green for both inheritance patterns.
Hereditary neuropathy or pain disorder v1.88 PCYT2 Dmitrijs Rots gene: PCYT2 was added
gene: PCYT2 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCYT2 were set to PMID: 35243002
Review for gene: PCYT2 was set to AMBER
Added comment: Two brother with axonal neuropathy reported in PMID: 35243002. In the same study, after reviewing previously published cases, other individuals (2/10) had sensory deficit / neuropathy: "Of 5 previously reported adult patients (age range of 20–59 years),2-6 nerve conduction studies were performed in 2 of them and reported as normal.3,4 Clinically, one of them had hypopallesthesia of the ankles,4 and the other had loss of vibration sense in the lower limbs and mild loss of proprioception in the feet".
Sources: Literature
Hereditary neuropathy or pain disorder v1.88 SLC12A6 Sarah Leigh commented on gene: SLC12A6: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.
Hereditary neuropathy or pain disorder v1.88 SPTBN4 Sarah Leigh commented on gene: SPTBN4
Hereditary neuropathy or pain disorder v1.88 NEMF Sarah Leigh commented on gene: NEMF
Hereditary neuropathy or pain disorder v1.88 AR_CAG Ivone Leong commented on STR: AR_CAG
Hereditary neuropathy or pain disorder v1.88 MME Ivone Leong Tag Q4_21_expert_review was removed from gene: MME.
Tag Q4_21_MOI was removed from gene: MME.
Tag Q4_21_NHS_review was removed from gene: MME.
Hereditary neuropathy or pain disorder v1.88 VWA1 Sarah Leigh commented on gene: VWA1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v1.88 POLR3B Sarah Leigh commented on gene: POLR3B
Hereditary neuropathy or pain disorder v1.88 PIGB Sarah Leigh commented on gene: PIGB
Hereditary neuropathy or pain disorder v1.88 MME Sarah Leigh commented on gene: MME
Hereditary neuropathy or pain disorder v1.88 HEXB Sarah Leigh commented on gene: HEXB
Hereditary neuropathy or pain disorder v1.88 HEXA Sarah Leigh commented on gene: HEXA
Hereditary neuropathy or pain disorder v1.88 GSN Sarah Leigh commented on gene: GSN
Hereditary neuropathy or pain disorder v1.88 C1orf194 Sarah Leigh commented on gene: C1orf194: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v1.87 MME Ivone Leong Mode of inheritance for gene MME was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v1.83 SORD Sarah Leigh commented on gene: SORD: NHS Genomic Medicine Service consideration - coverage and variant calling will be compromised by pseudogene issue.
Hereditary neuropathy or pain disorder v1.83 PNKP Sarah Leigh commented on gene: PNKP: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v1.83 SORD Sarah Leigh commented on gene: SORD
Hereditary neuropathy or pain disorder v1.80 SLC12A6 Sarah Leigh edited their review of gene: SLC12A6: Added comment: In reviewing SLC12A6 on the Intellectual disabily panel, it was suggested that this gene should be green on this panel (source NHS Genomic Medicine Service).; Changed rating: GREEN
Hereditary neuropathy or pain disorder v1.80 SLC5A6 Ian Berry gene: SLC5A6 was added
gene: SLC5A6 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A6 were set to PMID: 35013551
Phenotypes for gene: SLC5A6 were set to motor neuropathy
Penetrance for gene: SLC5A6 were set to Complete
Review for gene: SLC5A6 was set to GREEN
Added comment: Five individuals reported including three siblings with identical genotypes. Targeted therapy with biotin (therapeutic in other manifestations of this gene and in other biotin transporter deficiencies) improved phenotype in patients.
Sources: NHS GMS
Hereditary neuropathy or pain disorder v1.79 PDK3 Arina Puzriakova Added comment: Comment on list classification: At least two variants in three unrelated families reported (founder effect ruled out), as well as functional analyses conducted in patient fibroblasts, cell lines, and animal model. This supports a rating upgrade on this panel from Amber to Green at the next GMS panel update (tagged).
Hereditary neuropathy or pain disorder v1.78 MME Arina Puzriakova Tag Q4_21_expert_review tag was added to gene: MME.
Hereditary neuropathy or pain disorder v1.78 MME Arina Puzriakova Added comment: Comment on mode of inheritance: Heterozygous variants have been identified in >10 individuals with late-onset CMT2T. However, some variants have been found in control databases and family studies indicate incomplete penetrance, suggesting heterozygous variants only confer susceptibility. Nonetheless, sufficient cases have been reported in literature and both MOIs are listed in OMIM for this phenotype, and so inclusion of monoallelic inheritance on this panel will first be flagged for GMS review.
Hereditary neuropathy or pain disorder v1.78 MME Arina Puzriakova Mode of inheritance for gene: MME was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v1.77 MME Arina Puzriakova Tag adult-onset tag was added to gene: MME.
Tag Q4_21_MOI tag was added to gene: MME.
Hereditary neuropathy or pain disorder v1.77 MME Arina Puzriakova Publications for gene: MME were set to 26991897; 27588448
Hereditary neuropathy or pain disorder v1.76 MME Arina Puzriakova Phenotypes for gene: MME were changed from Charcot-Marie-Tooth disease, axonal, type 2T, 617017 to Charcot-Marie-Tooth disease, axonal, type 2T, OMIM:617017
Hereditary neuropathy or pain disorder v1.75 MME Arina Puzriakova Tag Q4_21_NHS_review tag was added to gene: MME.
Hereditary neuropathy or pain disorder v1.73 HEXB Arina Puzriakova Added comment: Comment on list classification: Neuropathy has been described in Sandhoff disease, particularly in adult-onset cases where this can be an initial finding and other symptoms may be more mild. Sufficient unrelated cases of neuropathy due to variants in this gene have been reported in literature (>3). Overall HEXB should be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v1.70 HEXA Arina Puzriakova Added comment: Comment on list classification: Neuronopathy and peripheral neuropathy have been described in Tay-Sachs disease, particularly in adult-onset cases where this can be an initial finding and other symptoms may be more mild. Sufficient unrelated cases of neuropathy due to variants in this gene have been reported in literature (>3). Overall HEXA should be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v1.68 MME Lindsey Vialard reviewed gene: MME: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27588448, 33144514; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary neuropathy or pain disorder v1.68 RFC1 Eleanor Williams commented on gene: RFC1: Copied this gene from the Hereditary ataxia - adult onset panel so that it is noted that the STR associated with this gene is relevant to the panel, NOT SNV/indels or deletions covering this gene. In PMID: 33969391 - Curro et al 2021 - they found that 43 patients (34%) with sensory neuropathy had biallelic AAGGG repeat expansions in RFC1and in none with sensory-motor neuropathy.
Hereditary neuropathy or pain disorder v1.67 HEXA Evan Reid gene: HEXA was added
gene: HEXA was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXA were set to PMID: 28739864; 18642377
Penetrance for gene: HEXA were set to Complete
Review for gene: HEXA was set to GREEN
Added comment: Both HEXA and HEXB autosomal recessive mutations can be associated with a late onset motor neuropathy, sometimes quite mild and sometimes resembling ALS. We missed diagnosis of a patient with a late onset motor neuropathy as HEXB is not on the neuropathy panel. I would suggest that HEXA and HEXB should both be included on this panel.
Sources: Literature
Hereditary neuropathy or pain disorder v1.65 FXN Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI to 'Biallelic' as monoallelic variants have not been associated with disease. Patients either harbour a homozygous expansion or are compound heterozygous for an expansion and a point mutation.
Hereditary neuropathy or pain disorder v1.64 TECPR2 Dmitrijs Rots gene: TECPR2 was added
gene: TECPR2 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECPR2 were set to PubMed: 33847017
Phenotypes for gene: TECPR2 were set to Hereditary sensory and autonomic neuropathy
Penetrance for gene: TECPR2 were set to unknown
Review for gene: TECPR2 was set to GREEN
Added comment: Neuser et al. (2021) reported clinical findings in 17 patients, including 2 sib pairs, from 15 families segregating HSAN9.
Sources: Literature
Hereditary neuropathy or pain disorder v1.63 COX20 Zornitza Stark gene: COX20 was added
gene: COX20 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: COX20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX20 were set to 33751098
Phenotypes for gene: COX20 were set to Neuropathy
Review for gene: COX20 was set to GREEN
gene: COX20 was marked as current diagnostic
Added comment: Well established association with mitochondrial disease, presentation with neuropathy reported PMID 33751098
Sources: Literature
Hereditary neuropathy or pain disorder v1.63 AIFM1 Arina Puzriakova commented on gene: AIFM1
Hereditary neuropathy or pain disorder v1.62 ABCA1 Arina Puzriakova commented on gene: ABCA1
Hereditary neuropathy or pain disorder v1.62 PIGB Arina Puzriakova Added comment: Comment on list classification: Axonal degenerative polyneuropathy and demyelinating sensorimotor polyneuropathy are observed in the more severely affected individuals with biallelic variants in this gene. There are sufficient cases with a relevant phenotype (5 individuals from 3 families) to rate as Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v1.60 C1orf194 Sarah Leigh edited their review of gene: C1orf194: Added comment: This green review is based on the review of Alexander Rossor (UCL Institute of Neurology), 8 Mar 2021, which was entered in error on the entry for C1orf94. The review is as follows: Two unrelated families, knock in mouse with relevant phenotype. Functional evidence for one variant only. Sources: Expert list.; Changed rating: GREEN
Hereditary neuropathy or pain disorder v1.60 C1orf194 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary neuropathy or pain disorder v1.59 C1orf94 Sarah Leigh Added comment: Comment on list classification: Curator deletion of this gene from this panel.
This gene has been added to this panel in error. The publications, phenotype and reviews are appropriate for C1orf194 and not for C1orf94.
Hereditary neuropathy or pain disorder v1.58 C1orf94 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary neuropathy or pain disorder v1.57 C1orf94 Sarah Leigh changed review comment from: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least 2 variants reported, together with a supportive mouse knock-out model.; to: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least 2 variants reported, together with a supportive mouse knock-out model (PMID: 31199454; 32592472).
Hereditary neuropathy or pain disorder v1.55 JAG1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Sullivan et al., 2020 (PMID:32065591) report two unrelated families with segregation, presenting vocal fold paresis. Knock in mouse model showed slight but nonsignificant reduction in compound muscle action potential and morphological assessments of the recurrent laryngeal nerve were normal. Mice did however display an increased frequency of axons with focally folded myelin. Notably, variants in JAG1 are associated with several phenotypes that have not included neuropathy and there was no history of cardiac, kidney, or liver disease in affected individuals in either of the two families discussed here (possibly different mechanisms of pathogenesis but further investigation may be warranted).

At this point there is not enough evidence to add this gene as diagnostic-grade; however, additional cases would corroborate this gene-disease association - rating Amber with 'watchlist' tag.
Hereditary neuropathy or pain disorder v1.52 TFG Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be assessed at the next GMS panel review. If the decision is made to include genes on this panel that are associated with neuropathy as part of a more complex phenotype, rather than isolated neuropathy, the MOI should be updated from 'monoallelic' only to 'both mono- and biallelic' .
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Monoallelic variants are associated with an adult-onset motor and sensory neuropathy (MIM# 604484), a disorder that is relevant to this panel. Biallelic variants cause a HSP (MIM# 615658) which also has been shown to involve peripheral neuropathy in complex cases. Both phenotypes have a sufficient number of unrelated cases (>3) reported to warrant a Green rating (updated publications list).
Hereditary neuropathy or pain disorder v1.46 FIG4 Sarah Leigh Deleted their comment
Hereditary neuropathy or pain disorder v1.45 FIG4 Sarah Leigh Added comment: Comment on phenotypes: Amyotrophic lateral sclerosis 11 OMIM:612577; amyotrophic lateral sclerosis type 11 MONDO:0012945; Charcot-Marie-Tooth disease, type 4J, OMIM:611228; Charcot-Marie-Tooth disease type 4J MONDO:0012640;Yunis Varon syndrome OMIM:216340;Yunis-Varon syndromeMONDO:0008995
Hereditary neuropathy or pain disorder v1.41 VWA1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary neuropathy or pain disorder v1.35 KIF1A Arina Puzriakova Added comment: Comment on mode of inheritance: Biallelic variants are associated with autonomic-sensory neuropathy (MIM# 614213). KIF1A is also associated HSP type 30 (MIM# 610357) which can be inherited recessively or dominantly, as well as NESCAV syndrome (MIM# 614255) caused by heterozygous variants in this gene - both monoallelic conditions have been shown to include peripheral sensorimotor neuropathy.

For this reason, the MOI could be changed from 'biallelic' to 'both mono- and biallelic' if it is decided to include genes on this panel that cause neuropathy as part of a more complex phenotype (tagged for GMS review)
Hereditary neuropathy or pain disorder v1.34 GSN Ivone Leong Added comment: Comment on list classification: New gene added by Dmitrijs Rots (RadboudUMC). This gene is associated with a phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Hereditary neuropathy or pain disorder v1.30 GSN Dmitrijs Rots gene: GSN was added
gene: GSN was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: GSN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GSN were set to PMID: 33499149; 26339870
Phenotypes for gene: GSN were set to Amyloidosis; cranial neuropathy; peripheral neuropathy; cutis laxa; cardiomyopathy; arrhytmia
Penetrance for gene: GSN were set to Complete
Review for gene: GSN was set to GREEN
gene: GSN was marked as current diagnostic
Added comment: Causes Amyloidosis, Finnish type with multisystem involvement. Peripheral and cranial neuropathy each reported in >70% of patients from >200 big cohort from Finland. PMID:26339870.
Sources: Literature
Hereditary neuropathy or pain disorder v1.26 POLR3B Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Djordjevic et al. 2021 (PMID:33417887) identified different de novo POLR3B variants in 6 unrelated individuals. EMG/NCSs for 5/6 individuals revealed predominantly demyelinating sensory and motor neuropathy. Other features included ID, ataxia, spasticity.

POLR3B is listed in G2P with a 'probable' disease confidence rating for this phenotype (POLR3B-related neurodevelopmental disorder - monoallelic), but is not yet in OMIM.

Overall, there is sufficient evidence to warrant a Green rating on this panel.
Hereditary neuropathy or pain disorder v1.25 CADM3 Zornitza Stark gene: CADM3 was added
gene: CADM3 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: CADM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CADM3 were set to 33889941
Phenotypes for gene: CADM3 were set to Charcot-Marie-Tooth disease
Review for gene: CADM3 was set to AMBER
Added comment: Three families reported with the same missense variant in CADM3, p.Tyr172Cys (one family de novo), with functional work in mice to show reduced expression of the mutant protein in axons and abnormal axonal organization.
Sources: Literature
Hereditary neuropathy or pain disorder v1.25 PIGB Dmitrijs Rots gene: PIGB was added
gene: PIGB was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: PIGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGB were set to 31256876
Phenotypes for gene: PIGB were set to intellectual disability; developmental delay; epilepsy; axonal neuropathy
Penetrance for gene: PIGB were set to Complete
Review for gene: PIGB was set to GREEN
gene: PIGB was marked as current diagnostic
Added comment: Murakami et al., reported 10 cases with biallelic PIGB variants with complex and severe phenotype, of whom 4 had peripheral neuropathy.
Sources: Literature
Hereditary neuropathy or pain disorder v1.25 VWA1 Ian Berry gene: VWA1 was added
gene: VWA1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS
Mode of inheritance for gene: VWA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA1 were set to PMID: 33559681
Phenotypes for gene: VWA1 were set to axonal hereditary motor neuropathy; myopathy
Penetrance for gene: VWA1 were set to unknown
Review for gene: VWA1 was set to GREEN
gene: VWA1 was marked as current diagnostic
Added comment: 17 individuals from 15 families, recurrent 10bp repeat allele causative in all patients. Detected in 100K so clearly tractable by WGS.
Sources: NHS GMS
Hereditary neuropathy or pain disorder v1.25 DHX9 Arina Puzriakova Added comment: Comment on list classification: Rating this gene as Red, but with a watchlist tag, until more evidence is available.
Hereditary neuropathy or pain disorder v1.24 DHX9 Arina Puzriakova gene: DHX9 was added
gene: DHX9 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Other
watchlist tags were added to gene: DHX9.
Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: DHX9 were set to Adult-onset axonal neuropathy
Added comment: Conference poster (Genomics of Rare Disease 2021) - 'DExH-box helicase 9 (DHX9) is a candidate hereditary axonal neuropathy gene' by Fatih et al, Baylor College of Medicine -

Report three unrelated individuals with adult-onset axonal neuropathy (age of onset: 41, 49, and 12 years old, respectively). Clinical features include limb weakness (3), muscle atrophy (2), diminished sensation in feet (2; plus in hands in 1 individual), ataxic gait (1), and painful neuropathy (1). All subjects exhibited neurogenic changes on EMG, and 2 cases also had normal or absent motor and sensory NCV.
Exome sequencing revealed distinct heterozygous variants in the DHX9 gene ([c.2537A>G, p.Asp846Gly]; [c.2510G>C, p.Arg837Thr]; [c.3763G>A, p.Ala1255Thr]). Segregation data was only available for one case, showing de novo occurrence. No functional data presented.

These variants have to be validated and currently DHX9 is deemed a candidate gene. No other publications in relation to this gene and phenotype are available in PubMed at this time.

Baylor College of Medicine POC: Dr. Daniel Calame, [email protected]
Sources: Other
Hereditary neuropathy or pain disorder v1.23 SPTAN1 Zornitza Stark gene: SPTAN1 was added
gene: SPTAN1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to 20493457; 22258530; 32811770
Phenotypes for gene: SPTAN1 were set to Hereditary motor neuropathy
Review for gene: SPTAN1 was set to GREEN
gene: SPTAN1 was marked as current diagnostic
Added comment: Gene previously associated with DEE.

PMID 32811770: 13 affected individuals from 4 families reported (nonsense variants) with AD distal hereditary motor neuropathy. Variable penetrance was noted and phenotype severity differs greatly between patients. Functional studies show NMD and reduced protein levels in patient cells.
Sources: Literature
Hereditary neuropathy or pain disorder v1.23 C12orf65 Catherine Snow commented on gene: C12orf65
Hereditary neuropathy or pain disorder v1.23 POLR3B Zornitza Stark gene: POLR3B was added
gene: POLR3B was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: POLR3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR3B were set to 33417887
Phenotypes for gene: POLR3B were set to Ataxia, spasticity, and demyelinating neuropathy
Review for gene: POLR3B was set to GREEN
Added comment: Note biallelic variants cause a leukodystrophy.

New MOI and new phenotype reported in PMID: 33417887: Six unrelated individuals with de novo missense variants and ataxia, spasticity, variable intellectual disability and epilepsy, and predominantly demyelinating sensory motor peripheral neuropathy.
Protein modeling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.
Sources: Literature
Hereditary neuropathy or pain disorder v1.23 SORD Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics) and recommended to be Green by David Hunt (Wessex Clinical Genetics Service).

"Given that this is a potentially treatable neuropathy (https://www.ucl.ac.uk/ion/news/2020/may/sord-neuropathy-accelerated-journey-gene-identification-effective-treatment-patients), I think that SORD should be included in the ‘Hereditary neuropathy NOT PMP22 copy number’ gene panel."

There is enough evidence to support a gene-disease association and this gene should be Green at the next review.
Hereditary neuropathy or pain disorder v1.21 PNKP Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Hereditary neuropathy or pain disorder v1.18 UBA5 Arina Puzriakova gene: UBA5 was added
gene: UBA5 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: UBA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBA5 were set to 32179706
Phenotypes for gene: UBA5 were set to Hypomyelinating neuropathy
Added comment: Note that UBA5 variants have been associated with a range of neurological phenotypes including epilepsy, ID and ataxia.

PMID: 32179706 (2020) - Five affected individuals from a consanguineous family presenting with a severe congenital neuropathy causing early death in infancy. Some in vitro functional data included. Due to early mortality, unclear whether additional features previously associated with UBA5 variants would have developed.
Sources: Literature
Hereditary neuropathy or pain disorder v1.17 SPTBN4 Arina Puzriakova Added comment: Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team) it has been agreed to add this gene as Amber, awaiting review by the GMS specialist group (added 'for-review' tag).

Although neuropathy is reported in at least 5 unrelated cases with biallelic SPTBN4 variants, the phenotype relevance requires review due to the more limited scope of this panel.
Hereditary neuropathy or pain disorder v1.16 SPTBN4 Arina Puzriakova gene: SPTBN4 was added
gene: SPTBN4 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
for-review tags were added to gene: SPTBN4.
Mode of inheritance for gene: SPTBN4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN4 were set to 28540413; 28940097; 29861105; 31230720; 31857255; 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. Motor neuronopathy/axonopathy was reported in 5 unrelated families. A formal evaluation by EMG/NCS was not conducted in the rest but phenotypes did include hypotonia and hyporeflexia which could be suggestive of neuropathy.
Sources: Literature
Hereditary neuropathy or pain disorder v1.15 ITPR3 Zornitza Stark gene: ITPR3 was added
gene: ITPR3 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: ITPR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITPR3 were set to 32949214
Phenotypes for gene: ITPR3 were set to Charcot-Marie-Tooth disease
Review for gene: ITPR3 was set to AMBER
Added comment: Two unrelated families reported: variant segregated in four affected individuals in one family and was de novo in the second family where there was a single affected person. Some evidence for dominant-negative effect.
Sources: Literature
Hereditary neuropathy or pain disorder v1.15 NUDT2 Arina Puzriakova Added comment: Comment on list classification: Rating Amber as only 2 unrelated cases harbouring the same variant reported at present
Hereditary neuropathy or pain disorder v1.14 NUDT2 Arina Puzriakova commented on gene: NUDT2: Comment on tags: added 'founder-effect' tag - although authors state that they do not believe p.Ala63GlnfsTer3 to be a founder variant (one family of Mexican descent while the other of Cajun descent), this was not confirmed by haplotype analysis. Also added 'watchlist' tag in anticipation of further publications/clinical evidence to support association with this phenotype.
Hereditary neuropathy or pain disorder v1.13 NUDT2 Arina Puzriakova gene: NUDT2 was added
gene: NUDT2 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
watchlist, founder-effect tags were added to gene: NUDT2.
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to 27431290; 30059600; 33058507
Phenotypes for gene: NUDT2 were set to Sensorimotor polyneuropathy; Muscular hypotonia; Intellectual disability; no OMIM number
Review for gene: NUDT2 was set to AMBER
Added comment: - PMID: 33058507 (2020) - Three patients from two families harbouring the same homozygous variant (c.186del, p.Ala63GlnfsTer3). Affected individuals present distal upper and lower extremity weakness due to a sensorimotor polyneuropathy with demyelinating and/or axonal features.
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A further 4 Saudi families (7 affected individuals) with a different homozygous NUDT2 variant (c.34C> T, p.Arg12) have been published elsewhere (PMID: 27431290, 30059600), however neuropathy was not reported in these cases.
Sources: Literature
Hereditary neuropathy or pain disorder v1.12 NEMF Arina Puzriakova Added comment: Comment on list classification: Rating Amber but there is sufficient evidence to promote to Green at the next GMS panel update (added 'for-review' tag) - axonal neuropathy reported in all formally assessed cases (at least 4 with biallelic variants)
Hereditary neuropathy or pain disorder v1.11 NEMF Arina Puzriakova Added comment: Comment on mode of inheritance: Set MOI to 'Biallelic' as only 1 case with a monoallelic variant described at present. The 'watchlist' tag has been added while further evidence is gathered to establish whether or not there is a wider association with monoallelic variants and disease.
Hereditary neuropathy or pain disorder v1.10 NEMF Arina Puzriakova gene: NEMF was added
gene: NEMF was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
watchlist, for-review tags were added to gene: NEMF.
Mode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEMF were set to 32934225; 33048237
Phenotypes for gene: NEMF were set to Hypotonia; Axonal neuropathy; Ataxia; Abnormal brain imaging; Global developmental delay; Intellectual disability; Kyphosis; Scoliosis; Tremor; Respiratory distress
Review for gene: NEMF was set to GREEN
Added comment: Currently not associated with any phenotype in OMIM (last edited on 04/01/2017) or Gene2Phenotype.

Gene added and expert reviewed on Intellectual Disability panel:
https://panelapp.genomicsengland.co.uk/panels/285/gene/NEMF/


- PMID: 32934225 (2020) - 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M)), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M). The authors provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration.


- PMID: 33048237 (2020) - 13 affected individuals from 5 unrelated families presenting with a spectrum of central and peripheral neurological involvement. Peripheral systemic neurological manifestations such as impaired eye movements, limb weakness, and axonal polyneuropathy were found in families 1, 2 and 5 - however, only 2 sibs from family 2 had a precise diagnosis for polyneuropathies. Knockdown studies in cultured mouse primary cortical neurons showed a significant decrease in axon length and impaired synapse development.
Sources: Literature
Hereditary neuropathy or pain disorder v1.8 GBF1 Zornitza Stark gene: GBF1 was added
gene: GBF1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: GBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GBF1 were set to 32937143
Phenotypes for gene: GBF1 were set to Axonal Neuropathy
Review for gene: GBF1 was set to GREEN
gene: GBF1 was marked as current diagnostic
Added comment: Four unrelated families with individuals affected by sporadic or dominant Distal hereditary motor neuropathies (HMNs) or axonal Charcot-Marie-Tooth neuropathy (CMT2). 3 missense variants (1 de novo) and 1 nonsense variant (de novo). Age of onset varied from childhood (nonsense variant) to 50s. Authors observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals.
Sources: Literature
Hereditary neuropathy or pain disorder v1.8 C1orf194 Arina Puzriakova changed review comment from: PMID: 32592472 (2020) - Another knockout mouse model by same research group, demonstrating defects in motor and sensory functions, myelination abnormalities, peripheral nerve loss and muscle atrophy.; to: PMID: 32592472 (2020) - An additional knockout mouse model by same research group, demonstrating defects in motor and sensory functions, myelination abnormalities, peripheral nerve loss and muscle atrophy.
Hereditary neuropathy or pain disorder v1.8 C1orf194 Arina Puzriakova edited their review of gene: C1orf194: Added comment: PMID: 32592472 (2020) - Another knockout mouse model by same research group, demonstrating defects in motor and sensory functions, myelination abnormalities, peripheral nerve loss and muscle atrophy.; Changed publications: 32592472; Changed phenotypes: Charcot-Marie-Tooth
Hereditary neuropathy or pain disorder v1.7 C1orf194 Arina Puzriakova Added comment: Comment on list classification: This is has been added with an Amber rating, in accordance with the expert review by Zornitza Stark.
Hereditary neuropathy or pain disorder v1.6 ACOX1 Zornitza Stark gene: ACOX1 was added
gene: ACOX1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: ACOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACOX1 were set to 32169171
Phenotypes for gene: ACOX1 were set to Mitchell syndrome, MIM# 618960
Review for gene: ACOX1 was set to GREEN
gene: ACOX1 was marked as current diagnostic
Added comment: Mono-allelic variants (recurrent de novo missense, N237S) associated with Mitchell syndrome (MITCH): a progressive disorder characterised by episodic demyelination, sensorimotor polyneuropathy, and hearing loss. By contrast, bi-allelic variants cause a peroxisomal disorder characterised by neonatal hypotonia, seizures, apnoeic spells, delayed psychomotor development, and neurologic regression.
Sources: Literature
Hereditary neuropathy or pain disorder v1.6 SLC12A6 Sarah Leigh commented on gene: SLC12A6: For-review tag has been added as it maybe appropriate to change the MOI to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next major review, to ensure that de novo heterozgous variants are identified.
Hereditary neuropathy or pain disorder v1.6 SLC12A6 Sarah Leigh commented on gene: SLC12A6
Hereditary neuropathy or pain disorder v1.5 YARS Sarah Leigh commented on gene: YARS
Hereditary neuropathy or pain disorder v1.5 EMILIN1 Zornitza Stark gene: EMILIN1 was added
gene: EMILIN1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: EMILIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EMILIN1 were set to 31978608; 26462740
Phenotypes for gene: EMILIN1 were set to Peripheral neuropathy; aortic aneurysm
Review for gene: EMILIN1 was set to AMBER
Added comment: Missense mutations identified in two families. First family, proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Variant segregated with disease in the affected proband, mother, and son. Second family, father and three affected children showed amyotrophy and weakness of the distal lower limbs, dating back to early childhood. Some functional studies performed in patient fibroblasts and zebrafish, however these were not conclusive as the two missense mutations are at different locations within the protein.
Sources: Literature
Hereditary neuropathy or pain disorder v1.4 SORD Zornitza Stark gene: SORD was added
gene: SORD was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SORD were set to 32367058
Phenotypes for gene: SORD were set to Neuropathy
Review for gene: SORD was set to GREEN
gene: SORD was marked as current diagnostic
Added comment: 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG
(p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state .
Sources: Literature
Hereditary neuropathy or pain disorder v1.4 C1orf194 Zornitza Stark gene: C1orf194 was added
gene: C1orf194 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: C1orf194 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: C1orf194 were set to 31199454
Phenotypes for gene: C1orf194 were set to Charcot-Marie-Tooth disease, intermediate or demyelinating
Review for gene: C1orf194 was set to AMBER
Added comment: Two unrelated families with missense variants, one with intermediate CMT, the other with demyelinating CMT. Different phenotypic manifestations may relate to different mechanism, but this remains to be fully elucidated. Supportive mouse model.
Sources: Literature
Hereditary neuropathy or pain disorder v1.4 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JAG1 were set to 32065591; 25707699
Phenotypes for gene: JAG1 were set to Peripheral neuropathy
Mode of pathogenicity for gene: JAG1 was set to Other
Review for gene: JAG1 was set to GREEN
Added comment: Two unrelated families reported with CMT type 2. Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Pre-existing rat model.
Sources: Literature
Hereditary neuropathy or pain disorder v1.4 VAPB Zornitza Stark gene: VAPB was added
gene: VAPB was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Expert list
Mode of inheritance for gene: VAPB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VAPB were set to 15372378; 32162544; 28993872; 28173107; 26566915
Phenotypes for gene: VAPB were set to Adult proximal spinal muscular atrophy, autosomal dominant; dHMN/dSMA; Spinal muscular atrophy, late-onset, Finkel type, MIM# 182980
Review for gene: VAPB was set to GREEN
Added comment: p.P56S variant found in multiple families from different ethnicities but additional variant also reported; functional data.
Sources: Expert list
Hereditary neuropathy or pain disorder v1.4 UBA1 Zornitza Stark gene: UBA1 was added
gene: UBA1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Expert list
Mode of inheritance for gene: UBA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: UBA1 were set to 18179898
Phenotypes for gene: UBA1 were set to Spinal muscular atrophy, X-linked 2, infantile MIM#301830
Review for gene: UBA1 was set to GREEN
gene: UBA1 was marked as current diagnostic
Added comment: Five families reported, gene is Green on the Paediatric motor neuropathies panel.
Sources: Expert list
Hereditary neuropathy or pain disorder v1.4 SCO2 Zornitza Stark gene: SCO2 was added
gene: SCO2 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Expert list
Mode of inheritance for gene: SCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCO2 were set to 29351582
Phenotypes for gene: SCO2 were set to axonal Charcot-Marie-Tooth disease
Review for gene: SCO2 was set to AMBER
Added comment: Two unrelated cases with compound heterozygous variants and a CMT phenotype. Cardiomyopathy not present.
Sources: Expert list
Hereditary neuropathy or pain disorder v1.0 WARS Louise Daugherty commented on gene: WARS: Added new-gene-name tag, new approved HGNC gene symbol for WARS is WARS1
Hereditary neuropathy or pain disorder v1.0 GARS Louise Daugherty Deleted their comment
Hereditary neuropathy or pain disorder v1.0 GARS Louise Daugherty commented on gene: GARS: Added new-gene-name tag, new approved HGNC gene symbol for GARS is GARS1
Hereditary neuropathy or pain disorder v1.0 AARS Louise Daugherty commented on gene: AARS: Added new-gene-name tag, new approved HGNC gene symbol for AARS is AARS1
Hereditary neuropathy or pain disorder v1.0 SEPT9 Louise Daugherty commented on gene: SEPT9: Added new-gene-name tag, new approved HGNC gene symbol for SEPT9 is SEPTIN9
Hereditary neuropathy or pain disorder v0.107 ABCA1 Louise Daugherty changed review comment from: Comment on list classification: Changed from Amber to Green - is a very rare condition, the primary feature can be neuropathy so if abnormalities of lipids or tonsils are missed or not present the diagnosis will not be made. However if there is a second panel to go to after the primary neuropathy panel and it is on it then it should still be diagnosed as long as a patient with primary neuropathy only would still be eligible for the more syndromic panel.; to: Comment on list classification: Changed from Amber to Green - recommendation from Genomics England clinical ream - is a very rare condition, the primary feature can be neuropathy so if abnormalities of lipids or tonsils are missed or not present the diagnosis will not be made. However if there is a second panel to go to after the primary neuropathy panel and it is on it then it should still be diagnosed as long as a patient with primary neuropathy only would still be eligible for the more syndromic panel.
Hereditary neuropathy or pain disorder v0.107 ABCA1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green - is a very rare condition, the primary feature can be neuropathy so if abnormalities of lipids or tonsils are missed or not present the diagnosis will not be made. However if there is a second panel to go to after the primary neuropathy panel and it is on it then it should still be diagnosed as long as a patient with primary neuropathy only would still be eligible for the more syndromic panel.
Hereditary neuropathy or pain disorder v0.106 VCP Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber from recommendation from Alex Rossor - only two published cases of VCP and neuropathy. P.Glu185Lys is absent form GNOMAD but p.Glu185Asp is present 4 times. I don’t think there have been any more cases. Might it be better as Amber for neuropathy?
Hereditary neuropathy or pain disorder v0.104 AR_CAG Louise Daugherty Added comment: Comment on list classification: changed rating : It was agreed that the 10 STRs submitted by Alex Rossor should be on the WGS panel only, with the exception of AR, which should be on both- so this STR was upgraded to Green - R78 has no mention of age in the directory, and will mostly be used for non-syndromic adult cases.
Hereditary neuropathy or pain disorder v0.92 FBXO38 Louise Daugherty changed review comment from: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope but limited evidence / SMA - limited evidence, some functional work but not strong - Amber? 2 families one very large segregating gene, possibly green if test Group supports rating?; to: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope but limited evidence / SMA - limited evidence, some functional work but not strong - Amber? 2 families one very large segregating gene, possibly green if test Group supports rating?
Hereditary neuropathy or pain disorder v0.91 DNAJB2 Louise Daugherty changed review comment from: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)/ New evidence/re-evaluation of evidence - promotion to Green? Reviewed initially as Amber due to single reported variant in 2016, however now multiple case series Frontiers in Molecular biosciences doi: 10.3389/fmolb.2016.00081 cites 10 cases (PMID: 28018906); to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)/ New evidence/re-evaluation of evidence - promotion to Green? Reviewed initially as Amber due to single reported variant in 2016, however now multiple case series Frontiers in Molecular biosciences doi: 10.3389/fmolb.2016.00081 cites 10 cases (PMID: 28018906) recessive CMT/ HMN.
Hereditary neuropathy or pain disorder v0.91 DNAJB2 Louise Daugherty changed review comment from: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)/ New evidence/re-evaluation of evidence - promotion to Green? Reviewed initially as Amber due to single reported variant in 2016, however now multiple case series Frontiers in Molecular biosciences doi: 10.3389/fmolb.2016.00081 cites 10 cases. ; to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)/ New evidence/re-evaluation of evidence - promotion to Green? Reviewed initially as Amber due to single reported variant in 2016, however now multiple case series Frontiers in Molecular biosciences doi: 10.3389/fmolb.2016.00081 cites 10 cases (PMID: 28018906)
Hereditary neuropathy or pain disorder v0.91 DNAJB2 Louise Daugherty changed review comment from: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)/ Green for larger panel only as main phenotype is distal SMA; AR to provide further references; to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)/ New evidence/re-evaluation of evidence - promotion to Green? Reviewed initially as Amber due to single reported variant in 2016, however now multiple case series Frontiers in Molecular biosciences doi: 10.3389/fmolb.2016.00081 cites 10 cases.
Hereditary neuropathy or pain disorder v0.90 AR_CAG Louise Daugherty STR: AR_CAG was added
STR: AR_CAG was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Expert Review
STR tags were added to STR: AR_CAG.
Mode of inheritance for STR: AR_CAG was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for STR: AR_CAG were set to Spinal and bulbar muscular atrophy or Kennedy diseases 313200
Review for STR: AR_CAG was set to GREEN
Added comment: New Green STR submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group. This STR has been rated Amber until further discussion with the Neurology Test Group on 21st June 2019- although appropriate to have on this panel, they can be more late-onset, this panel is used for children so needs further discussion with the GLHs and Genomics England Clinical team before upgrading to Green.
Sources: Expert Review
Hereditary neuropathy or pain disorder v0.86 ZFYVE26 Louise Daugherty commented on gene: ZFYVE26: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - HSP with neuropathy / Broader phenotype: HSP
Hereditary neuropathy or pain disorder v0.86 XRCC1 Louise Daugherty commented on gene: XRCC1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope but limited evidence / Broader phenotype: SCA26, 2 cases in OMIM
Hereditary neuropathy or pain disorder v0.86 XPA Louise Daugherty commented on gene: XPA: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: XP/de Sanctis-Cacchione syndrome - does only this form of XP have neurological features?
Hereditary neuropathy or pain disorder v0.86 XK Louise Daugherty commented on gene: XK: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: McLeod syndrome, note adult onset
Hereditary neuropathy or pain disorder v0.86 VPS13A Louise Daugherty commented on gene: VPS13A: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: Choreoacanthocytosis
Hereditary neuropathy or pain disorder v0.86 VCP Louise Daugherty edited their review of gene: VCP: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: ALS+/-FTD; unclear whether also causes CMT - Amber? Very rare but I think include as Green as reasonable evidence for distal myopathy/neuropathy; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.86 TWNK Louise Daugherty commented on gene: TWNK: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: mitochondrial, comment that neuropathy is not common
Hereditary neuropathy or pain disorder v0.86 TTPA Louise Daugherty commented on gene: TTPA: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - ataxia with neuropathy / Broader phenotype: ataxia with vitamin E deficiency More likely to present as ataxia on ataxia panel
Hereditary neuropathy or pain disorder v0.86 TRPA1 Louise Daugherty commented on gene: TRPA1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Episodic pain syndrome - within scope of panel? Only 1 family in OMIM Agree not enough evidence
Hereditary neuropathy or pain disorder v0.86 SURF1 Louise Daugherty commented on gene: SURF1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - mitochondrial / Broader phenotype: Leigh syndrome with neuropathy
Hereditary neuropathy or pain disorder v0.86 SUCLA2 Louise Daugherty commented on gene: SUCLA2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: Leigh-like syndrome, neuropathy 'in a minority of patients'
Hereditary neuropathy or pain disorder v0.86 SPG7 Louise Daugherty commented on gene: SPG7: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype submitted by Alex Rossor, but 2 reviews say no clear association with neuropathy
Hereditary neuropathy or pain disorder v0.86 SPAST Louise Daugherty commented on gene: SPAST: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - HSP with neuropathy / Broader phenotype (HSP)
Hereditary neuropathy or pain disorder v0.86 SOX10 Louise Daugherty commented on gene: SOX10: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: PERIPHERAL DEMYELINATING NEUROPATHY, CENTRAL DYSMYELINATION, WAARDENBURG SYNDROME, AND HIRSCHSPRUNG DISEASE; PCWH (Shah-Waardenburg syndrome, neurologic variant)
Hereditary neuropathy or pain disorder v0.86 SLC25A46 Louise Daugherty commented on gene: SLC25A46: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: Optic atrophy and progressive visual loss in the 1st decade, then spasticity, cerebellar ataxia, sensory-motor axonal neuropathy
Hereditary neuropathy or pain disorder v0.86 SLC25A19 Louise Daugherty commented on gene: SLC25A19: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - epilepsy/encephalopathy with neuropathy / Broader phenotype: episodic encephalopathy with progressive axonal neuropathy; common mutation in Amish and 1 other unrelated family in OMIM
Hereditary neuropathy or pain disorder v0.86 SCYL1 Louise Daugherty commented on gene: SCYL1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope but limited evidence / Overlap: SCA21 - 2 cases in OMIM, sufficient evidence?
Hereditary neuropathy or pain disorder v0.86 SCN10A Louise Daugherty edited their review of gene: SCN10A: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Episodic pain syndrome - within scope of panel? 2 cases het missense variants (1 segregating in 2 family members) and functional evidence in OMIM - sufficient for Green if within scope? If SCN9A is on the panel then this and similar genes should be on too. Recommend Green; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.86 SCARB2 Louise Daugherty commented on gene: SCARB2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: epilepsy and renal failure, 'rarely' sensorimotor neuropathy
Hereditary neuropathy or pain disorder v0.86 PTRH2 Louise Daugherty commented on gene: PTRH2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope but limited evidence / Broad phenotype but limited evidence? Only 2 cases in OMIM
Hereditary neuropathy or pain disorder v0.86 PTPN11 Louise Daugherty commented on gene: PTPN11: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broad phenotype - Noonan syndrome - is hypertrophic neuropathy an important feature?
Hereditary neuropathy or pain disorder v0.86 PTEN Louise Daugherty commented on gene: PTEN: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broad phenotype - is neuropathy a common feature?
Hereditary neuropathy or pain disorder v0.86 PRKCG Louise Daugherty commented on gene: PRKCG: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Neuropathy rare feature - Amber
Hereditary neuropathy or pain disorder v0.86 POLR3A Louise Daugherty commented on gene: POLR3A: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - ataxia with neuropathy / Broader phenotype: spastic ataxia with abnormal nerve conduction in 8/14 cases
Hereditary neuropathy or pain disorder v0.86 PNPLA6 Louise Daugherty commented on gene: PNPLA6: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: Natalie no evidence of clear association with neuropathy
Hereditary neuropathy or pain disorder v0.86 PNKP Louise Daugherty commented on gene: PNKP: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotype
Hereditary neuropathy or pain disorder v0.86 PMM2 Louise Daugherty commented on gene: PMM2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: CDG1a
Hereditary neuropathy or pain disorder v0.86 PLP1 Louise Daugherty commented on gene: PLP1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: Pelizaeus-Merbacher/Spastic paraplegia 2 - is neuropathy a feature?
Hereditary neuropathy or pain disorder v0.86 PEX10 Louise Daugherty commented on gene: PEX10: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: Zellweger, is neuropathy only associated with this gene?
Hereditary neuropathy or pain disorder v0.86 PDYN Louise Daugherty commented on gene: PDYN: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: SCA with mild neuropathy
Hereditary neuropathy or pain disorder v0.86 OPA3 Louise Daugherty commented on gene: OPA3: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: 3-methylglutaconic aciduria type III
Hereditary neuropathy or pain disorder v0.86 OPA1 Louise Daugherty commented on gene: OPA1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - mitochondrial / Broader mitochondrial phenotype
Hereditary neuropathy or pain disorder v0.86 NAGA Louise Daugherty commented on gene: NAGA: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: Schindler disease
Hereditary neuropathy or pain disorder v0.84 ZFYVE26 Louise Daugherty commented on gene: ZFYVE26: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 XRCC1 Louise Daugherty commented on gene: XRCC1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 XPA Louise Daugherty commented on gene: XPA: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 XK Louise Daugherty commented on gene: XK: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 VPS13A Louise Daugherty commented on gene: VPS13A: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 VCP Louise Daugherty commented on gene: VCP: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 TWNK Louise Daugherty commented on gene: TWNK: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 TTPA Louise Daugherty commented on gene: TTPA: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 TRPA1 Louise Daugherty commented on gene: TRPA1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SURF1 Louise Daugherty commented on gene: SURF1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SUCLA2 Louise Daugherty commented on gene: SUCLA2: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SPG7 Louise Daugherty commented on gene: SPG7: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SPAST Louise Daugherty commented on gene: SPAST: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SOX10 Louise Daugherty commented on gene: SOX10: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SLC25A46 Louise Daugherty commented on gene: SLC25A46: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SLC25A19 Louise Daugherty commented on gene: SLC25A19: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SCYL1 Louise Daugherty commented on gene: SCYL1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SCN10A Louise Daugherty commented on gene: SCN10A: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 SCARB2 Louise Daugherty commented on gene: SCARB2: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PTRH2 Louise Daugherty commented on gene: PTRH2: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PTPN11 Louise Daugherty commented on gene: PTPN11: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PTEN Louise Daugherty commented on gene: PTEN: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PRKCG Louise Daugherty commented on gene: PRKCG: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 POLR3A Louise Daugherty commented on gene: POLR3A: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PNPLA6 Louise Daugherty commented on gene: PNPLA6: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PNKP Louise Daugherty commented on gene: PNKP: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PMM2 Louise Daugherty commented on gene: PMM2: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PLP1 Louise Daugherty commented on gene: PLP1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PEX10 Louise Daugherty commented on gene: PEX10: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 PDYN Louise Daugherty commented on gene: PDYN: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 OPA3 Louise Daugherty commented on gene: OPA3: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 OPA1 Louise Daugherty commented on gene: OPA1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.84 NAGA Louise Daugherty commented on gene: NAGA: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.83 SLC25A19 Louise Daugherty Deleted their comment
Hereditary neuropathy or pain disorder v0.82 MYH14 Louise Daugherty commented on gene: MYH14: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - minor feature / Hearing loss enough evidence for Green; 1 family with hearing loss & neuropathy in literature, are there additional unpublished families?
Hereditary neuropathy or pain disorder v0.82 MYH14 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.81 MTTP Louise Daugherty commented on gene: MTTP: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - Causes a progressive sensory neuropathy related to vitamin E deficiency as part of a complex multisystem disorder
Hereditary neuropathy or pain disorder v0.81 MTTP Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.80 MT-TL1 Louise Daugherty commented on gene: MT-TL1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - mitochondrial / Broader phenotype but mitochondrial gene (MELAS) - discuss
Hereditary neuropathy or pain disorder v0.80 MT-TL1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.79 MT-RNR1 Louise Daugherty commented on gene: MT-RNR1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - mitochondrial / Broader phenotype but mitochondrial gene - discuss
Hereditary neuropathy or pain disorder v0.79 MT-RNR1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.78 MMACHC Louise Daugherty commented on gene: MMACHC: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - methylmalonic acidemia & homcysteinuria
Hereditary neuropathy or pain disorder v0.78 MMACHC Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.77 LYST Louise Daugherty commented on gene: LYST: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - Chediak-Higashi (albinism, immune deficiency)
Hereditary neuropathy or pain disorder v0.77 LYST Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.76 KCNA2 Louise Daugherty commented on gene: KCNA2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - ataxia with neuropathy / Broader phenotype - epilepsy & ataxia, neuropathy only in one family - is neuropathy a consistent feature?
Hereditary neuropathy or pain disorder v0.76 KCNA2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.75 IARS2 Louise Daugherty commented on gene: IARS2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - mitochondrial / Broader phenotype
Hereditary neuropathy or pain disorder v0.75 IARS2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.74 PPOX Louise Daugherty commented on gene: PPOX: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype: variegate porphyria. As per CPOX usually presents more acutely but management implications. Promote to Green as management implications
Hereditary neuropathy or pain disorder v0.74 PPOX Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.73 HMBS Louise Daugherty commented on gene: HMBS: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - acute intermittent porphyria As per CPOX usually presents more acutely but management implications. Promote to Green as management implications
Hereditary neuropathy or pain disorder v0.73 CPOX Louise Daugherty changed review comment from: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - porphyria, can present similar to AIP according to Alex Promote to Green as management implications; to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - porphyria, can present similar to AIP according to Alex Rossor. Promote to Green as management implications
Hereditary neuropathy or pain disorder v0.73 HMBS Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.72 HADHB Louise Daugherty commented on gene: HADHB: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - mitochondrial / Broader phenotype - mitochondrial trifunctional protein deficiency
Hereditary neuropathy or pain disorder v0.72 HADHB Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.71 HADHA Louise Daugherty commented on gene: HADHA: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - mitochondrial / Broader phenotype - mitochondrial trifunctional protein deficiency
Hereditary neuropathy or pain disorder v0.71 HADHA Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.70 GJC2 Louise Daugherty commented on gene: GJC2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - HSP with neuropathy / Broader phenotype - HSP/hypomyelinating leucodystrophy with neuropathy
Hereditary neuropathy or pain disorder v0.70 GJC2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.69 GBA2 Louise Daugherty commented on gene: GBA2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - HSP with neuropathy / Broader phenotype - HSP with neuropathy
Hereditary neuropathy or pain disorder v0.69 GBA2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.68 TYMP Louise Daugherty commented on gene: TYMP: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.68 TYMP Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.67 TUBB3 Louise Daugherty commented on gene: TUBB3: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.67 TUBB3 Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.66 SLC12A6 Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.65 SLC12A6 Louise Daugherty commented on gene: SLC12A6: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.65 SACS Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.64 SACS Louise Daugherty commented on gene: SACS: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.64 POLG Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.63 POLG Louise Daugherty commented on gene: POLG: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.63 PHYH Louise Daugherty commented on gene: PHYH: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.63 PEX7 Louise Daugherty commented on gene: PEX7: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.63 PDHA1 Louise Daugherty commented on gene: PDHA1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.63 GLA Louise Daugherty commented on gene: GLA: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.63 GAN Louise Daugherty commented on gene: GAN: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.63 PHYH Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.62 PEX7 Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.61 PDHA1 Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.60 GLA Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.59 GAN Louise Daugherty Added comment: Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Hereditary neuropathy or pain disorder v0.58 GALC Louise Daugherty commented on gene: GALC: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - Krabbe disease
Hereditary neuropathy or pain disorder v0.58 GALC Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.57 FXN Louise Daugherty commented on gene: FXN: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - ataxia with neuropathy / Rate as Green if STR Green Should be on ataxia panels
Hereditary neuropathy or pain disorder v0.57 FXN Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.56 FLVCR1 Louise Daugherty commented on gene: FLVCR1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - ataxia with neuropathy / Broader phenotype - ataxia & RP. Agree more suited to ataxia panel
Hereditary neuropathy or pain disorder v0.56 FLVCR1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.55 FBXO38 Louise Daugherty commented on gene: FBXO38: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope but limited evidence / SMA - limited evidence, some functional work but not strong - Amber? 2 families one very large segregating gene, possibly green if test Group supports rating?
Hereditary neuropathy or pain disorder v0.55 FBXO38 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.54 FAM126A Louise Daugherty commented on gene: FAM126A: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype: leukodystrophy
Hereditary neuropathy or pain disorder v0.54 FAM126A Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.53 FAH Louise Daugherty commented on gene: FAH: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype: Tyrosinemia, acute episodes of neuropathy similar to AIP
Hereditary neuropathy or pain disorder v0.53 FAH Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.52 ETFDH Louise Daugherty commented on gene: ETFDH: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - minor feature / Broader phenotype: Glutaric acidemia IIc - minor feature
Hereditary neuropathy or pain disorder v0.52 ETFDH Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.51 ERCC8 Louise Daugherty commented on gene: ERCC8: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - Cockayne syndrome
Hereditary neuropathy or pain disorder v0.51 ERCC8 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.50 ERCC6 Louise Daugherty commented on gene: ERCC6: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) Extension of panel scope - syndrome with non-neurological features / Broader phenotype - Cockayne syndrome
Hereditary neuropathy or pain disorder v0.50 ERCC6 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.49 ELP1 Louise Daugherty changed review comment from: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Familial dysautonomia - appropriate for panel Keep green; to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Familial dysautonomia - appropriate for panel. autonomic neuropathy - relevant to both panels (narrow and broad). Keep green
Hereditary neuropathy or pain disorder v0.49 ELP1 Louise Daugherty commented on gene: ELP1: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Familial dysautonomia - appropriate for panel Keep green
Hereditary neuropathy or pain disorder v0.49 ELP1 Louise Daugherty edited their review of gene: ELP1: Added comment: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.49 DNAJC3 Louise Daugherty commented on gene: DNAJC3: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - minor feature / Broader phenotype - ataxia & hearing loss - only 1 family in OMIM - more evidence? Complex disorder not pure neuropathy
Hereditary neuropathy or pain disorder v0.49 DNAJC3 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.48 CYP27A1 Louise Daugherty changed review comment from: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca). Although Extension of panel scope - syndrome with non-neurological features / Broader phenotype - cerebrotendinous xanthomatosis, it was noted that it was good to pick up early; to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca). Although Extension of panel scope - syndrome with non-neurological features / Broader phenotype - cerebrotendinous xanthomatosis, it was noted that it was good to pick up early so advised Green rating over Amber for R57 panel
Hereditary neuropathy or pain disorder v0.48 CYP27A1 Louise Daugherty changed review comment from: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - cerebrotendinous xanthomatosis; to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca). Although Extension of panel scope - syndrome with non-neurological features / Broader phenotype - cerebrotendinous xanthomatosis, it was noted that it was good to pick up early
Hereditary neuropathy or pain disorder v0.47 DEGS1 Louise Daugherty commented on gene: DEGS1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - leukodystrophy with neuropathy
Hereditary neuropathy or pain disorder v0.47 DEGS1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.46 DARS2 Louise Daugherty commented on gene: DARS2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - mitochondrial / Mitochondrial gene - extension to phenotype to include isolated neuropathy
Hereditary neuropathy or pain disorder v0.46 DARS2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.45 CYP27A1 Louise Daugherty commented on gene: CYP27A1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - cerebrotendinous xanthomatosis
Hereditary neuropathy or pain disorder v0.45 CYP27A1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.44 CTDP1 Louise Daugherty commented on gene: CTDP1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype (dysmorphic, cataract) - founder mutation in Roma populations, intronic
Hereditary neuropathy or pain disorder v0.44 CTDP1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.42 CPOX Louise Daugherty edited their review of gene: CPOX: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - porphyria, can present similar to AIP according to Alex Promote to Green as management implications; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.42 CPOX Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.41 COA7 Louise Daugherty commented on gene: COA7: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) Extension of panel scope - ataxia with neuropathy / Broader phenotype - SCA with axonal neuropathy
Hereditary neuropathy or pain disorder v0.41 COA7 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.40 WARS Louise Daugherty edited their review of gene: WARS: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green/ Additional evidence: 3 cases in literature with same variant on diff haplotypes and postulated dom neg effect; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.40 VRK1 Louise Daugherty changed review comment from: Gene rated Green: From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)
New evidence/re-evaluation of evidence - promotion to Green / Additional evidence: PMID:30847374 cites 2 other cases with neuropathy & unpublished evidence; to: Gene rated Amber: From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)
New evidence/re-evaluation of evidence - promotion to Green / Additional evidence: PMID:30847374 cites 2 other cases with neuropathy & unpublished evidence.
Hereditary neuropathy or pain disorder v0.39 VRK1 Louise Daugherty commented on gene: VRK1: Gene rated Green: From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)
New evidence/re-evaluation of evidence - promotion to Green / Additional evidence: PMID:30847374 cites 2 other cases with neuropathy & unpublished evidence
Hereditary neuropathy or pain disorder v0.38 TRIM2 Louise Daugherty commented on gene: TRIM2: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green / Consider for Green with functional data? 2 families with missense variants; no new publications since 2015
Hereditary neuropathy or pain disorder v0.38 SYT2 Louise Daugherty changed review comment from: Gene rated Red : From feedback from Genomics England Clinical team (Anna de Burca). Congenital myasthenia gene; currently Green on Congenital myaesthenic syndrome Panel so recommend leave as Red on the R78 panel, but promote to Green on larger panel for WGS; to: Gene rated Red : From feedback from Genomics England Clinical team (Anna de Burca). 3 families and functional data according to Natalie's review but more of a myastheia phenotype but overlaps with CMT . Congenital myasthenia gene; currently Green on Congenital myaesthenic syndrome Panel so recommend leave as Red on the R78 panel, but promote to Green on larger panel for WGS.
Hereditary neuropathy or pain disorder v0.37 SYT2 Louise Daugherty changed review comment from: Gene rated Red : From feedback from Genomics England Clinical team (Anna de Burca). Congenital myasthenia gene; currently Red on congenital myasthenic syndrome panel but Oxford have given Green review for that panel so suggest promote on the congenital myasthenic syndrome panel, leave as Red on the R78 panel, but promote to Green on larger panel for WGS; to: Gene rated Red : From feedback from Genomics England Clinical team (Anna de Burca). Congenital myasthenia gene; currently Green on Congenital myaesthenic syndrome Panel so recommend leave as Red on the R78 panel, but promote to Green on larger panel for WGS
Hereditary neuropathy or pain disorder v0.37 SYT2 Louise Daugherty commented on gene: SYT2: Gene rated Red : From feedback from Genomics England Clinical team (Anna de Burca). Congenital myasthenia gene; currently Red on congenital myasthenic syndrome panel but Oxford have given Green review for that panel so suggest promote on the congenital myasthenic syndrome panel, leave as Red on the R78 panel, but promote to Green on larger panel for WGS
Hereditary neuropathy or pain disorder v0.37 PRNP Louise Daugherty changed review comment from: Gene rated red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotype. AlexRossor felt that there was sufficient evidence that this can cause a neuropathy but that this would be an unusual presentation – suggest that AR provide additional evidence for a Green rating on the WGS panel but make Red for the R78 panel; to: Gene rated red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotype. Alex Rossor felt that there was sufficient evidence that this can cause a neuropathy but that this would be an unusual presentation – suggest that Alex Rossor provide additional evidence for a Green rating on the WGS panel but make Red for the R78 panel
Hereditary neuropathy or pain disorder v0.37 SETX Louise Daugherty changed review comment from: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / James Polke Red review but no comment?? Pretty rare for this to present as a dominant juvenile ALS phenotype but three different mutations reported. Probably reasonable to keep as green but presumably in ALS panel; to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / James Polke Red review but no comment?? Pretty rare for this to present as a dominant juvenile ALS phenotype but three different mutations reported. Probably reasonable to keep as green but presumably in ALS panel. SETX had been reviewed by James Polke as Red but he had not left a comment, since he was not on the call, agreed that this gene be left as Green unless James provides an explanation for his Red review
Hereditary neuropathy or pain disorder v0.37 SETX Louise Daugherty changed review comment from: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / James Polke Red review but no comment?? Pretty rare for this to present as a dominant juvenile ALS phenotype but three different mutations reported. Probably reasonable to keep as green but presumably in ALS panel; to: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / James Polke Red review but no comment?? Pretty rare for this to present as a dominant juvenile ALS phenotype but three different mutations reported. Probably reasonable to keep as green but presumably in ALS panel
Hereditary neuropathy or pain disorder v0.37 PRNP Louise Daugherty changed review comment from: Gene rated red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotype; to: Gene rated red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotype. AlexRossor felt that there was sufficient evidence that this can cause a neuropathy but that this would be an unusual presentation – suggest that AR provide additional evidence for a Green rating on the WGS panel but make Red for the R78 panel
Hereditary neuropathy or pain disorder v0.37 PRNP Louise Daugherty changed review comment from: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
AlexRossor felt that there was sufficient evidence that this can cause a neuropathy but that this would be an unusual presentation – suggest that AR provide additional evidence for a Green rating on the WGS panel but make Red for the R78 panel; to: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.37 SLC5A7 Louise Daugherty edited their review of gene: SLC5A7: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green? / Limited evidence? See Natalie review but AR says multiple families; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.37 SETX Louise Daugherty edited their review of gene: SETX: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / James Polke Red review but no comment?? Pretty rare for this to present as a dominant juvenile ALS phenotype but three different mutations reported. Probably reasonable to keep as green but presumably in ALS panel; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.37 SBF1 Louise Daugherty edited their review of gene: SBF1: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green / New evidence: 1 more family - promote to Green; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.37 PRNP Louise Daugherty commented on gene: PRNP: Gene rated red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotype
Hereditary neuropathy or pain disorder v0.37 PMP2 Louise Daugherty edited their review of gene: PMP2: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green / New evidence - green; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.37 NEFH Louise Daugherty commented on gene: NEFH: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green? / New CMT gene, 2 families & functional evidence in OMIM
Hereditary neuropathy or pain disorder v0.36 MCM3AP Louise Daugherty edited their review of gene: MCM3AP: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) New evidence/re-evaluation of evidence - promotion to Green/ New evidence - PMID:28633435; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.36 GNB4 Louise Daugherty commented on gene: GNB4: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green / CMT - new evidence Agree promote to Green
Hereditary neuropathy or pain disorder v0.36 DST Louise Daugherty commented on gene: DST: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) . New evidence/re-evaluation of evidence - promotion to Green / New evidence - upgrade to Green? New evidence promote to Green
Hereditary neuropathy or pain disorder v0.36 DRP2 Louise Daugherty commented on gene: DRP2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green? 2 cases but functional studies don't show features of neuropathy - Amber? More evidence needed
Hereditary neuropathy or pain disorder v0.36 DNAJB2 Louise Daugherty commented on gene: DNAJB2: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart)/ Green for larger panel only as main phenotype is distal SMA; AR to provide further references
Hereditary neuropathy or pain disorder v0.36 DCTN1 Louise Daugherty edited their review of gene: DCTN1: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) . New evidence/re-evaluation of evidence - promotion to Green / New evidence - upgrade to Green; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.36 DCTN1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.35 ATP1A1 Louise Daugherty edited their review of gene: ATP1A1: Added comment: Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green / New gene - 7 unrelated families (2018) Agree promote to Green; Changed rating: GREEN
Hereditary neuropathy or pain disorder v0.35 ARHGEF10 Louise Daugherty commented on gene: ARHGEF10: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / One published family plus functional evidence (NB. Bristol review although Green acknowledges limited evidence) - demote
Hereditary neuropathy or pain disorder v0.35 ATL3 Louise Daugherty commented on gene: ATL3: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / Limited evidence highlighted by Natalie - same variant in 2 families and other variant didn't segregate - downgrade to Amber? Agree downgrade due to lack of evidence
Hereditary neuropathy or pain disorder v0.35 CNTNAP1 Louise Daugherty commented on gene: CNTNAP1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - congenital hypomyelinating neuropathy, arthrogryposis, severe dev delay
Hereditary neuropathy or pain disorder v0.35 CNTNAP1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.34 CD59 Louise Daugherty commented on gene: CD59: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype: haemolytic anaemia, strokes and relapsing immune-mediated demyelinating neuropathy
Hereditary neuropathy or pain disorder v0.34 CD59 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.33 C12orf65 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.32 BCKDHB Louise Daugherty commented on gene: BCKDHB: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype - Maple syrup urine disease
Hereditary neuropathy or pain disorder v0.32 BCKDHB Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.31 BAG3 Louise Daugherty commented on gene: BAG3: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - myopathy with neuropathy / Broader phenotype - not reviewed by Alex in this round but previously reviewed as Green; myofibrillar myopathy, sufficient evidence for neuropathy?
Hereditary neuropathy or pain disorder v0.31 BAG3 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.30 B4GALNT1 Louise Daugherty commented on gene: B4GALNT1: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - HSP with neuropathy / Broader phenotype: HSP gene but can be associated with neuropathy.
Hereditary neuropathy or pain disorder v0.30 B4GALNT1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.29 ATM Louise Daugherty commented on gene: ATM: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - ataxia with neuropathy / Broader phenotype - biallelic only (cancer risk)
Hereditary neuropathy or pain disorder v0.29 ATM Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.28 ARSA Louise Daugherty commented on gene: ARSA: Gene rated as Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Metachromatic leukodystrophy - broader phenotype
Hereditary neuropathy or pain disorder v0.28 ARSA Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.27 APTX Louise Daugherty commented on gene: APTX: Gene remains rated as Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - ataxia with neuropathy / Broader phenotype: Ataxia with oculomotor apraxia
Hereditary neuropathy or pain disorder v0.27 APTX Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.25 APOA1 Louise Daugherty commented on gene: APOA1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.25 APOA1 Louise Daugherty changed review comment from: Gene remains rated as Red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart).. Extension of panel scope - minor feature. Amyloidosis - most cases visceral amyloidosis but 1 family with neurological phenotype- rate Red.
R78 was going to be broadened to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. Subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for this panel to be restricted to genes that are associated with isolated neuropathy.; to: Gene remains rated as Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart).. Extension of panel scope - minor feature. Amyloidosis - most cases visceral amyloidosis but 1 family with neurological phenotype- rate Red.
Hereditary neuropathy or pain disorder v0.24 AP1S1 Louise Daugherty commented on gene: AP1S1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.24 AP1S1 Louise Daugherty changed review comment from: Gene remains rated as Red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope but limited evidence / Congenital onset, Mental retardation, Enteropathy (severe congenital diarrhoea), Deafness, sensory-motor Neuropathy with intermediate conduction velocities, Ichthyosis, Keratoderma - OMIM 4 families from Quebec with same splice site mutation - rated Red
R78 was going to be broadened to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. Subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for this panel to be restricted to genes that are associated with isolated neuropathy.; to: Gene remains rated as Amber: From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope but limited evidence / Congenital onset, Mental retardation, Enteropathy (severe congenital diarrhoea), Deafness, sensory-motor Neuropathy with intermediate conduction velocities, Ichthyosis, Keratoderma - OMIM 4 families from Quebec with same splice site mutation
Hereditary neuropathy or pain disorder v0.24 AGXT Louise Daugherty changed review comment from: Gene remains rated as Red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - minor feature / Gene well established to cause PH1 Primary Hyperoxaluria (green). 2 reports of neuropathy - enough cases?- rated Red
R78 was going to be broadened to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. Subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for this panel to be restricted to genes that are associated with isolated neuropathy.; to: Gene remains rated Amber: From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - minor feature / Gene well established to cause PH1 Primary Hyperoxaluria (green). 2 reports of neuropathy - enough cases?
Hereditary neuropathy or pain disorder v0.24 AGXT Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.21 AGTPBP1 Louise Daugherty commented on gene: AGTPBP1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.21 AGTPBP1 Louise Daugherty changed review comment from: Gene remains rated as Red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart).Extension of panel scope - syndrome with non-neurological features / Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy - complex phenotype - overlap with ID - rated Red.
R78 was going to be broadened to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. Subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for this panel to be restricted to genes that are associated with isolated neuropathy.; to: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart).Extension of panel scope - syndrome with non-neurological features / Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy - complex phenotype - overlap with ID
Hereditary neuropathy or pain disorder v0.21 ABCA1 Louise Daugherty commented on gene: ABCA1: The gene has changed ratings as the panel to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/
Hereditary neuropathy or pain disorder v0.21 ABCA1 Louise Daugherty changed review comment from: Comment on list classification: Amber gene: Feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features/ Peripheral neuropathy with low HDL.
The gene has changed ratings as the panel to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/

; to: Comment on list classification: Amber gene: Feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features/ Peripheral neuropathy with low HDL.
Hereditary neuropathy or pain disorder v0.21 ABHD12 Louise Daugherty changed review comment from: Gene remains rated as Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Polyneuropathy with SNCV (slow nerve conduction velocity?), sensorineuronal hearing loss, retinitis pigmentosa, spastic paraplegia, ataxia - rated Red.
; to: Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Polyneuropathy with SNCV (slow nerve conduction velocity?), sensorineuronal hearing loss, retinitis pigmentosa, spastic paraplegia, ataxia
Hereditary neuropathy or pain disorder v0.21 ABHD12 Louise Daugherty commented on gene: ABHD12: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.21 ABHD12 Louise Daugherty changed review comment from: Gene remains rated as Red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Polyneuropathy with SNCV (slow nerve conduction velocity?), sensorineuronal hearing loss, retinitis pigmentosa, spastic paraplegia, ataxia - rated Red.
R78 was going to be broadened to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. Subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for this panel to be restricted to genes that are associated with isolated neuropathy.; to: Gene remains rated as Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Polyneuropathy with SNCV (slow nerve conduction velocity?), sensorineuronal hearing loss, retinitis pigmentosa, spastic paraplegia, ataxia - rated Red.
Hereditary neuropathy or pain disorder v0.21 WARS Louise Daugherty commented on gene: WARS: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.21 VRK1 Louise Daugherty commented on gene: VRK1: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.21 TRIM2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.20 SYT2 Louise Daugherty commented on gene: SYT2: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.20 SLC5A7 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.19 SETX Louise Daugherty commented on gene: SETX: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.19 SBF1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.17 PRNP Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
AlexRossor felt that there was sufficient evidence that this can cause a neuropathy but that this would be an unusual presentation – suggest that AR provide additional evidence for a Green rating on the WGS panel but make Red for the R78 panel
Hereditary neuropathy or pain disorder v0.16 PMP2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.15 NEFH Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.14 MCM3AP Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.13 GNB4 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.12 DST Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.11 DRP2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.10 DNAJB2 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.9 ATP1A1 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.8 ATL3 Louise Daugherty Added comment: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.7 ARHGEF10 Louise Daugherty changed review comment from: Comment on list classification: The gene has changed ratings as the panel to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.; to: Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.7 ARHGEF10 Louise Daugherty Added comment: Comment on list classification: The gene has changed ratings as the panel to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Hereditary neuropathy or pain disorder v0.6 ABCA1 Louise Daugherty changed review comment from: Comment on list classification: Amber gene: Feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features/ Peripheral neuropathy with low HDL.
The gene has changed ratings as the panel to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents

; to: Comment on list classification: Amber gene: Feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features/ Peripheral neuropathy with low HDL.
The gene has changed ratings as the panel to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/
Hereditary neuropathy or pain disorder v0.6 ABCA1 Louise Daugherty changed review comment from: Comment on list classification: Amber gene: Feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features/ Peripheral neuropathy with low HDL
The gene has changed ratings as the panel that was going to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents

; to: Comment on list classification: Amber gene: Feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features/ Peripheral neuropathy with low HDL.
The gene has changed ratings as the panel to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents
Hereditary neuropathy or pain disorder v0.5 ABCA1 Louise Daugherty changed review comment from: Comment on list classification: Changed from Red to Green: Feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features/ Peripheral neuropathy with low HDL - rated Green.
R78 was going to be broadened to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. Subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for this panel to be restricted to genes that are associated with isolated neuropathy.; to: Comment on list classification: Amber gene: Feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features/ Peripheral neuropathy with low HDL
The gene has changed ratings as the panel that was going to be used for R78 was going to be broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents
Hereditary neuropathy or pain disorder v0.5 ABCA1 Louise Daugherty Deleted their comment
Hereditary neuropathy or pain disorder v0.1 TRPV4 Ellen McDonagh gene: TRPV4 was added
gene: TRPV4 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Illumina TruGenome Clinical Sequencing Services,London North GLH,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Green,South West GLH,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: TRPV4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRPV4 were set to 20037586
Phenotypes for gene: TRPV4 were set to Hereditary motor and sensory neuropathy, type IIc, 606071
Mode of pathogenicity for gene: TRPV4 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary neuropathy or pain disorder v0.1 SPTLC2 Ellen McDonagh gene: SPTLC2 was added
gene: SPTLC2 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Illumina TruGenome Clinical Sequencing Services,London North GLH,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Green,South West GLH,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: SPTLC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPTLC2 were set to 20920666
Phenotypes for gene: SPTLC2 were set to Hereditary Sensory and Autonomic Neuropathy, Type IC; Neuropathy, hereditary sensory and autonomic, type IC, 613640
Mode of pathogenicity for gene: SPTLC2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Hereditary neuropathy or pain disorder v0.1 SIGMAR1 Ellen McDonagh gene: SIGMAR1 was added
gene: SIGMAR1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Expert Review,Expert Review Green
Mode of inheritance for gene: SIGMAR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIGMAR1 were set to PMID: 26088964 is a commentary on PMID: 25678561 raising a lack of evidence for SIGMARI to be pathogenic, and that previous reports of patients with SIGMARI variants were also shown to harbour C9orf72 expansions. PMID: 26088963 - in reply, authors state that there is in vitro and in vivo evidence, and expression evidence, and that a case reported did not have the C9orf72 expansion; PubMed: 21842496 - E102Q variant identified in a Saudi Arabian family to be associated with amyotrophic lateral sclerosis 16, juvenile; PMID: 26078401 - c.151+1G>T variant in SIGMARI resulted in a 60 bp deletion in the transcript, and segrated with the distal hereditary motor neuropathy in a Chinese family.; PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis and c.672*31A>G (rs4879809) - the C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls
Hereditary neuropathy or pain disorder v0.1 MME Ellen McDonagh gene: MME was added
gene: MME was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Other,Expert Review Green
Mode of inheritance for gene: MME was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MME were set to 26991897; 27588448
Phenotypes for gene: MME were set to Charcot-Marie-Tooth disease, axonal, type 2T, 617017