Activity
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| Hereditary neuropathy or pain disorder v8.37 | COL6A3 |
Luke Stuart changed review comment from: COL6A3 is associated with Bethlem myopathy 1C, OMIM #620726; Dystonia 27, OMIM #616411; Ullrich congenital muscular dystrophy 1C, OMIM #620728. As reviewed by Alexander Rossor, Villar-Quiles et al., 2026 (PMID 42520849) described Thirty-seven affected individuals from 32 families harbouring biallelic COL6A3 variants. All carried the recurrent c.7447A>G p.(Lys2483Glu) allele either in homozygosity (24 patients) or compound heterozygosity with a second (often truncating) COL6A3 variant (13 patients). Phase was confirmed in 28 cases. Genetic testing was performed via whole-exome sequencing (WES) or whole-genome sequencing (WGS) in 30 patients, and next-generation sequencing (NGS)-based myopathy panel in 7. The cohort demonstrated a consistent distal motor neuropathy-like/neuromyopathic phenotype with neurogenic electrophysiological findings. Most patients presented in the first decade of life with an abnormal gait and frequent falls (54%), delayed motor milestones (32%) and foot deformities (19%). Predominant distal weakness was present in 46% of patients. Muscle biopsy (n=12) demonstrated features suggestive of neuropathic involvement in 4 (33%) and mixed neuropathic-myopathic features in 5 (42%). >70% of the patients showed motor conduction abnormalities, and needle EMG (n=31) revealed chronic neurogenic-like features in 84% and mixed neuromyogenic features in 13%. All patients carried the recurrent c.7447A>G p.(Lys2483Glu) variant and, therefore, despite the presence of a minority of compound heterozygous patients, it remains unclear whether the observed neuropathy-like phenotype represents a variant-specific effect. In summary, this study provides strong evidence that distal motor neuropathy and neuromyopathy are part of the COL6A3 phenotypic spectrum. A green rating is therefore recommended for the Hereditary neuropathy or pain disorder panel.; to: COL6A3 is associated with Bethlem myopathy 1C, OMIM #620726; Dystonia 27, OMIM #616411; Ullrich congenital muscular dystrophy 1C, OMIM #620728. As reviewed by Alexander Rossor, Villar-Quiles et al., 2026 (PMID 42520849) described Thirty-seven affected individuals from 32 families harbouring biallelic COL6A3 variants. All carried the recurrent c.7447A>G p.(Lys2483Glu) allele either in homozygosity (24 patients) or compound heterozygosity with a second (often truncating) COL6A3 variant (13 patients). Phase was confirmed in 28 cases. Genetic testing was performed via whole-exome sequencing (WES) or whole-genome sequencing (WGS) in 30 patients, and next-generation sequencing (NGS)-based myopathy panel in 7. COL6A3 c.7447A>G p.(Lys2483Glu) is present in Gnomad v4 at a frequency of 1158/ 1614090 alleles including 1 homozygote. The cohort demonstrated a consistent distal motor neuropathy-like/neuromyopathic phenotype with neurogenic electrophysiological findings. Most patients presented in the first decade of life with an abnormal gait and frequent falls (54%), delayed motor milestones (32%) and foot deformities (19%). Predominant distal weakness was present in 46% of patients. Muscle biopsy (n=12) demonstrated features suggestive of neuropathic involvement in 4 (33%) and mixed neuropathic-myopathic features in 5 (42%). >70% of the patients showed motor conduction abnormalities, and needle EMG (n=31) revealed chronic neurogenic-like features in 84% and mixed neuromyogenic features in 13%. All patients carried the recurrent c.7447A>G p.(Lys2483Glu) variant and, therefore, despite the presence of a minority of compound heterozygous patients, it remains unclear whether the observed neuropathy-like phenotype represents a variant-specific effect. In summary, this study provides strong evidence that distal motor neuropathy and neuromyopathy are part of the COL6A3 phenotypic spectrum. A green rating is therefore recommended for the Hereditary neuropathy or pain disorder panel. |
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| Hereditary neuropathy or pain disorder v8.37 | COL6A3 |
Luke Stuart changed review comment from: COL6A3 is associated with Bethlem myopathy 1C, OMIM #620726; Dystonia 27, OMIM #616411; Ullrich congenital muscular dystrophy 1C, OMIM #620728. As reviewed by Alexander Rossor, Villar-Quiles et al., 2026 (PMID 620728) described Thirty-seven affected individuals from 32 families harbouring biallelic COL6A3 variants. All carried the recurrent c.7447A>G p.(Lys2483Glu) allele either in homozygosity (24 patients) or compound heterozygosity with a second (often truncating) COL6A3 variant (13 patients). Phase was confirmed in 28 cases. Genetic testing was performed via whole-exome sequencing (WES) or whole-genome sequencing (WGS) in 30 patients, and next-generation sequencing (NGS)-based myopathy panel in 7. The cohort demonstrated a consistent distal motor neuropathy-like/neuromyopathic phenotype with neurogenic electrophysiological findings. Most patients presented in the first decade of life with an abnormal gait and frequent falls (54%), delayed motor milestones (32%) and foot deformities (19%). Predominant distal weakness was present in 46% of patients. Muscle biopsy (n=12) demonstrated features suggestive of neuropathic involvement in 4 (33%) and mixed neuropathic-myopathic features in 5 (42%). >70% of the patients showed motor conduction abnormalities, and needle EMG (n=31) revealed chronic neurogenic-like features in 84% and mixed neuromyogenic features in 13%. All patients carried the recurrent c.7447A>G p.(Lys2483Glu) variant and, therefore, despite the presence of a minority of compound heterozygous patients, it remains unclear whether the observed neuropathy-like phenotype represents a variant-specific effect. In summary, this study provides strong evidence that distal motor neuropathy and neuromyopathy are part of the COL6A3 phenotypic spectrum. A green rating is therefore recommended for the Hereditary neuropathy or pain disorder panel.; to: COL6A3 is associated with Bethlem myopathy 1C, OMIM #620726; Dystonia 27, OMIM #616411; Ullrich congenital muscular dystrophy 1C, OMIM #620728. As reviewed by Alexander Rossor, Villar-Quiles et al., 2026 (PMID 42520849) described Thirty-seven affected individuals from 32 families harbouring biallelic COL6A3 variants. All carried the recurrent c.7447A>G p.(Lys2483Glu) allele either in homozygosity (24 patients) or compound heterozygosity with a second (often truncating) COL6A3 variant (13 patients). Phase was confirmed in 28 cases. Genetic testing was performed via whole-exome sequencing (WES) or whole-genome sequencing (WGS) in 30 patients, and next-generation sequencing (NGS)-based myopathy panel in 7. The cohort demonstrated a consistent distal motor neuropathy-like/neuromyopathic phenotype with neurogenic electrophysiological findings. Most patients presented in the first decade of life with an abnormal gait and frequent falls (54%), delayed motor milestones (32%) and foot deformities (19%). Predominant distal weakness was present in 46% of patients. Muscle biopsy (n=12) demonstrated features suggestive of neuropathic involvement in 4 (33%) and mixed neuropathic-myopathic features in 5 (42%). >70% of the patients showed motor conduction abnormalities, and needle EMG (n=31) revealed chronic neurogenic-like features in 84% and mixed neuromyogenic features in 13%. All patients carried the recurrent c.7447A>G p.(Lys2483Glu) variant and, therefore, despite the presence of a minority of compound heterozygous patients, it remains unclear whether the observed neuropathy-like phenotype represents a variant-specific effect. In summary, this study provides strong evidence that distal motor neuropathy and neuromyopathy are part of the COL6A3 phenotypic spectrum. A green rating is therefore recommended for the Hereditary neuropathy or pain disorder panel. |
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| Hereditary neuropathy or pain disorder v8.37 | COL6A3 | Ida Ertmanska Tag Q3_26_NHS_review tag was added to gene: COL6A3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.37 | COL6A3 | Ida Ertmanska Tag Q3_26_promote_green tag was added to gene: COL6A3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.37 | COL6A3 | Ida Ertmanska Phenotypes for gene: COL6A3 were changed from motor neuropathy; myopathy to Motor peripheral neuropathy, MONDO:0002316 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.36 | COL6A3 | Ida Ertmanska Classified gene: COL6A3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.36 | COL6A3 | Ida Ertmanska Gene: col6a3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.35 | COL6A3 | Ida Ertmanska reviewed gene: COL6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Motor peripheral neuropathy, MONDO:0002316; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.31 | COL6A3 | Luke Stuart reviewed gene: COL6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 42520849; Phenotypes: Motor peripheral neuropathy, MONDO:0002316; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.31 | COL6A3 |
Alexander Rossor gene: COL6A3 was added gene: COL6A3 was added to Hereditary neuropathy or pain disorder. Sources: Expert list Mode of inheritance for gene: COL6A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COL6A3 were set to 42520849 Phenotypes for gene: COL6A3 were set to motor neuropathy; myopathy Mode of pathogenicity for gene: COL6A3 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: COL6A3 was set to GREEN Added comment: Case series of 35 patients showing evidence of both a peripheral motor neuropathy and myopathy Sources: Expert list |
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