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| Hereditary Neuropathy_CMT - isolated v1.52 | NARS |
Chris Ciotta changed review comment from: Three families reported in the literature with heterozygous NARS1 variants and an isolated peripheral neuropathy phenotype, lacking the global developmental delay, seizures and intellectual disability and more seen in the dominant and recessive neurodevelopmental disorder phenotypes listed in OMIM (MIM#619091 and MIM#619092). Beijer (2024) (PMID: 38495304): Two families with previously unreported missense variants and an isolated neuropathy phenotype. Segregation of this variant with disease also shown. Both missense variants severely reduced yeast growth compared to wildtype in a yeast rescue complementation assay. A mouse model expressing the p.Ser461Phe variant did not show any signs of peripheral neuropathy in mice heterozygous for this variant at multiple time points to 18 months of age. Theuriet (2024) (PMID: 38769024): A novel missense reported in a French family with distal hereditary motor neuropathy. A mother and two sons all with an isolated phenotype with no seizures or ID. Mother presented in 30s and two sons presented 5 and 3 with toe walking. A yeast model was also done here with this variant allowing for no growth compared to wildtype. Sources: Literature; to: Three families reported in the literature with heterozygous NARS1 variants and an isolated peripheral neuropathy phenotype, lacking the global developmental delay, seizures and intellectual disability and more seen in the dominant and recessive neurodevelopmental disorder phenotypes listed in OMIM (MIM#619091 and MIM#619092). Beijer (2024) (PMID: 38495304): Two families with previously unreported missense variants and an isolated neuropathy phenotype. Segregation of these variants with disease also shown. Both missense variants severely reduced yeast growth compared to wildtype in a yeast rescue complementation assay. A mouse model expressing the p.Ser461Phe variant did not show any signs of peripheral neuropathy in mice heterozygous for this variant at multiple time points to 18 months of age. Theuriet (2024) (PMID: 38769024): A novel missense reported in a French family with distal hereditary motor neuropathy. A mother and two sons all with an isolated phenotype with no seizures or ID. Mother presented in 30s and two sons presented 5 and 3 with toe walking. A yeast model was also done here with this variant allowing for no growth compared to wildtype. Sources: Literature |
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| Hereditary Neuropathy_CMT - isolated v1.52 | NARS |
Chris Ciotta gene: NARS was added gene: NARS was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature Mode of inheritance for gene: NARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NARS were set to PMID: 38495304; 38769024 Phenotypes for gene: NARS were set to Axonal neuropathy; Charcot-Marie-Tooth disease; distal hereditary motor neuropathy Review for gene: NARS was set to AMBER Added comment: Three families reported in the literature with heterozygous NARS1 variants and an isolated peripheral neuropathy phenotype, lacking the global developmental delay, seizures and intellectual disability and more seen in the dominant and recessive neurodevelopmental disorder phenotypes listed in OMIM (MIM#619091 and MIM#619092). Beijer (2024) (PMID: 38495304): Two families with previously unreported missense variants and an isolated neuropathy phenotype. Segregation of this variant with disease also shown. Both missense variants severely reduced yeast growth compared to wildtype in a yeast rescue complementation assay. A mouse model expressing the p.Ser461Phe variant did not show any signs of peripheral neuropathy in mice heterozygous for this variant at multiple time points to 18 months of age. Theuriet (2024) (PMID: 38769024): A novel missense reported in a French family with distal hereditary motor neuropathy. A mother and two sons all with an isolated phenotype with no seizures or ID. Mother presented in 30s and two sons presented 5 and 3 with toe walking. A yeast model was also done here with this variant allowing for no growth compared to wildtype. Sources: Literature |
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| Hereditary Neuropathy_CMT - isolated v1.39 | SORD | Sangavi Sivagnanasundram reviewed gene: SORD: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006246; Phenotypes: Charcot-Marie-Tooth disease (MONDO:0015626); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v1.30 | DHX9 |
Zornitza Stark gene: DHX9 was added gene: DHX9 was added to Hereditary Neuropathy_CMT - isolated. Sources: Literature Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DHX9 were set to 37467750 Phenotypes for gene: DHX9 were set to Charcot-Marie-Tooth disease, MONDO:0015626, DHX9-related Review for gene: DHX9 was set to GREEN Added comment: PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder (NDD) and three were reported with Charcot-Marie-Tooth disease (CMT). All 14 cases with NDD had developmental delay, of which eight were reported with intellectual disability (4 severe, 1 moderate, 3 mild). Two cases did not have ID, one had borderline ID and three cases were too young (0-5 years old). The three cases with CMT presented with adult-onset axonal neuropathy. LoF variants caused mild NDD phenotypes and nuclear localization signal (NLS) missense variants caused severe NDD. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress. Sources: Literature |
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| Hereditary Neuropathy_CMT - isolated v0.171 | SCN9A | Zornitza Stark Phenotypes for gene: SCN9A were changed from Erythermalgia, primary; Hereditary sensory and autonomic neuropathy type IID; HSAN/SFN to Erythermalgia, primary, MIM# 133020; Insensitivity to pain, congenital, MIM# 243000; Neuropathy, hereditary sensory and autonomic, type IID, MIM# 243000; Paroxysmal extreme pain disorder, MIM# 167400; Small fiber neuropathy,MIM# 133020 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.170 | SCN9A | Zornitza Stark reviewed gene: SCN9A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Erythermalgia, primary, MIM# 133020, Insensitivity to pain, congenital, MIM# 243000, Neuropathy, hereditary sensory and autonomic, type IID, MIM# 243000, Paroxysmal extreme pain disorder, MIM# 167400, Small fiber neuropathy,MIM# 133020; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.165 | DHTKD1 | Zornitza Stark changed review comment from: Comment on list classification: Two unrelated families and animal model.; to: Comment on list classification: Two unrelated families and animal model. Note bi-allelic variants are associated with a metabolic disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.47 | SORD | Zornitza Stark Phenotypes for gene: SORD were changed from isolated hereditary neuropathy to isolated hereditary neuropathy; Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDDPN), MIM#618912 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.46 | SORD | Zornitza Stark edited their review of gene: SORD: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.46 | SORD | Zornitza Stark reviewed gene: SORD: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDDPN), MIM#618912; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.44 | SORD | Seb Lunke Marked gene: SORD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.44 | SORD | Seb Lunke Gene: sord has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.44 | SORD | Seb Lunke Classified gene: SORD as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.44 | SORD | Seb Lunke Gene: sord has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.43 | SORD | Seb Lunke edited their review of gene: SORD: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary Neuropathy_CMT - isolated v0.43 | SORD |
Seb Lunke gene: SORD was added gene: SORD was added to Hereditary Neuropathy_CMT - isolated. 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 isolated hereditary neuropathy 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 |
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