Activity

Filter

Cancel
Date Panel Item Activity
28 actions
Hereditary neuropathy or pain disorder v7.38 CHRNA3 Ida Ertmanska Phenotypes for gene: CHRNA3 were changed from Familial Autonomic Ganglionopathy to Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, OMIM:191800; autonomic nervous system disorder, MONDO:0001292
Hereditary neuropathy or pain disorder v7.36 CHRNA3 Dmitrijs Rots gene: CHRNA3 was added
gene: CHRNA3 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: CHRNA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA3 were set to PMID: 33947782; 37161764
Phenotypes for gene: CHRNA3 were set to Familial Autonomic Ganglionopathy
Review for gene: CHRNA3 was set to GREEN
Added comment: 4 cases from 3 families are reported with biallelic LoF variants in the CHRNA3 causing familial dysautonomia:
PMID: 33947782;37161764
Sources: Literature
Hereditary neuropathy or pain disorder v6.103 FLVCR1 Sarah Leigh Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, 609033; Retinitis pigmentosa, sensory ganglionopathy and abnormal posterior columns on MRI to Ataxia, posterior column, with retinitis pigmentosa, OMIM:609033
Hereditary neuropathy or pain disorder v6.14 NDUFS6 Eleanor Williams changed review comment from: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome in previous reports (PubMed: 19259137 and PubMed: 15372108).

There is now phenotypic expansion with 4 families reported with a less severe phenotype. 3 families share a common variant.

PMID: 38459834 - Camila Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.; to: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome in previous reports (PubMed: 19259137 Spiegal et al 2009 and PubMed: 15372108 Kirby et al 2004, PMID: 30948790 - Rouzier et al 2019, PMID: 22474353 Ke et al 2012).

There is now phenotypic expansion with 5 families reported with a less severe phenotype. 4 families share a common variant.

PMID: 38459834 - Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.

PMID: 38217609 - Gangfuß et al 2024 - identified a homozygous variant (c.309 + 5 G > A) in NDUFS6 in one male patient aged 10 with axonal neuropathy accompanied by loss of small fibers in skin biopsy. The patient also showed optic atrophy and borderline intellectual disability.
Hereditary neuropathy or pain disorder v5.86 TRMT5 Arina Puzriakova Added comment: Comment on list classification: New gene added to the panel by Alexander Rossor (UCL Institute of Neurology). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Associated with relevant phenotype in OMIM, but not associated with phenotype in G2P. At least 3 variants reported in at least three cases, together with supportive functional studies.

Phenotype is characterised as a highly variable multisystemic disorder, ranging from hypotonia and GDD in infancy to exercise intolerance and muscle weakness in early adulthood. Peripheral neuropathy is a universal feature in all cases. Various other neurological features such as spasticity, cerebellar signs and seizures, and involvement of other organ systems, including the heart, pancreas, and kidney may also be observed.
Hereditary neuropathy or pain disorder v5.16 GAN Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: GAN.
Tag Q2_24_NHS_review was removed from gene: GAN.
Hereditary neuropathy or pain disorder v5.16 GAN Achchuthan Shanmugasundram reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v5.15 GAN Achchuthan Shanmugasundram Source Expert Review Green was added to GAN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.92 GAN Arina Puzriakova Publications for gene: GAN were set to 1106248
Hereditary neuropathy or pain disorder v3.91 GAN Arina Puzriakova Classified gene: GAN as Amber List (moderate evidence)
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 v3.91 GAN Arina Puzriakova Gene: gan has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.90 GAN Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: GAN.
Tag Q2_24_NHS_review tag was added to gene: GAN.
Hereditary neuropathy or pain disorder v3.90 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from Giant axonal neuropathy-1 to Giant axonal neuropathy-1, OMIM:256850
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 v3.88 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 v3.83 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 v3.82 GAN Tracy Lester reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301315; Phenotypes: neuropathy, intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
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 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 v0.59 GAN Louise Daugherty Classified gene: GAN as Amber List (moderate evidence)
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 v0.59 GAN Louise Daugherty Gene: gan has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v0.1 SURF1 Ellen McDonagh gene: SURF1 was added
gene: SURF1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH
Mode of inheritance for gene: SURF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SURF1 were set to Leigh syndrome, due to COX IV deficiency, 256000; Leigh syndrome (early onset progressive neurodegeneration of the brain stem, basal ganglia and spinal cord), neuropathy with SNCV
Hereditary neuropathy or pain disorder v0.1 FLVCR1 Ellen McDonagh gene: FLVCR1 was added
gene: FLVCR1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH
Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLVCR1 were set to 21070897
Phenotypes for gene: FLVCR1 were set to Ataxia, posterior column, with retinitis pigmentosa, 609033; Retinitis pigmentosa, sensory ganglionopathy and abnormal posterior columns on MRI
Hereditary neuropathy or pain disorder v0.1 GAN Ellen McDonagh gene: GAN was added
gene: GAN was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Green,South West GLH
Mode of inheritance for gene: GAN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAN were set to 1106248
Phenotypes for gene: GAN were set to Giant axonal neuropathy-1
Hereditary neuropathy or pain disorder v0.1 ABCA1 Ellen McDonagh gene: ABCA1 was added
gene: ABCA1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Expert Review Green
Mode of inheritance for gene: ABCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA1 were set to 29582519
Phenotypes for gene: ABCA1 were set to pain, paresthesias, anaesthesia; Multifocal relapsing mononeuropathies. Orange tonsils, organomegaly; Tangier disease, 205400