Congenital muscular dystrophy and congenital myopathy
Gene: COL4A1
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Additional comments from reviewing GLHs: 'Not sufficient evidence for CMD, however decision may be different for other panels as been implicated with muscle cramps. Remain amber'Created: 2 May 2024, 3:45 p.m. | Last Modified: 2 May 2024, 3:45 p.m.
Panel Version: 0.229
Sarah Leigh (Genomics England Curator) reviewing this gene on the old GMS Congenital muscular dystrophy panel on 28 Sep 2023 notes (rated green): 'Based on the review published by Rannikmäe et al (PMID: 32842921), numerous COL4A1 variants have been associated with muscle phenotypes (supplementary table IIIA).'
Publications: 32842921Created: 21 Dec 2023, 8:47 p.m. | Last Modified: 21 Dec 2023, 8:47 p.m.
Panel Version: 0.200
Comment on list classification: Sarah Leigh (Genomics England Curator) reviewing this gene on the old GMS Congenital muscular dystrophy panel on 28 Sep 2023 notes: 'There is enough evidence for this gene to be rated GREEN at the next major review.'Created: 21 Dec 2023, 8:45 p.m. | Last Modified: 21 Dec 2023, 8:45 p.m.
Panel Version: 0.200
Gavin Ryan (West Midlands Regional Genetics Laboratory) reviewing this gene on the old GMS Congenital muscular dystrophy panel on 16 Jun 2023 notes (rated Green):'Previous publications have demonstrated multiple individuals with early onset muscle cramps associated with HANAC syndrome (see publications by Plaisier et al). Some individuals do not demonstrate, or are subclinical, for some of the features of this disorder. As part of WGS GMS testing we identified an individual with muscle cramps (but not other features yet of HANAC syndrome) with request for Other rare neuromuscular disorders superpanel and a de novo likely pathogenic variant identified in this gene. This patient would not have had this variant identified if trio de novo analysis had not been performed. All previous pathogenic variants associated with HANAC syndrome identified in exons 24 and 25 of COL4A1, affecting glycine residues. Other disorders associated with this gene have variants distributed elsewhere within the gene.'
Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications: 18160688; 20818663Created: 21 Dec 2023, 8:40 p.m. | Last Modified: 21 Dec 2023, 8:40 p.m.
Panel Version: 0.197
Publications
Initial gene list (Congenital Muscular Dystrophy Gene Panel 207-London South GLH.xlsx) collated by Rachael Mein, Viapath Guy's Hospital February 2019 on behalf of London South GLH for the GMS Neurology specialist test group.Created: 29 Apr 2019, 3:37 p.m.
Although convincing functional evidence that this could be a CMD gene, it is not enough to make it green (only one report to date)Created: 25 Jan 2017, 4:06 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Walker Warburg Syndrome
Publications
Comment on list classification: Keep as amber for now due to borderline evidence - see reviewer comments.Created: 27 Jan 2017, 1:42 p.m.
Comment on list classification: Promoted to amber due to comments from reviewer - seems to be borderline evidence. 2 patients out of 27 with CMD were found to have be heterozygous for a rare missense variant in COL4A1 at a conserved residue; one of these variants, Q1316E, resulted in impaired COL4A1 secretion in transfected HT1080 Human fibrosarcoma cells.Created: 25 Jan 2017, 11:08 a.m.
2 patients reported, good mouse model, likely CMD gene (Labelle-Dumais, PLOS 2011) will check with Guys re more casesCreated: 19 Dec 2016, 12:02 p.m.
2 patients reported, good mouse model, likely CMD gene (Labelle-Dumais, PLOS 2011) will check with Guys re more casesCreated: 19 Dec 2016, noon
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
walker warburg syndrome, muscle eye brain disease
Tag Q3_23_promote_green was removed from gene: COL4A1. Tag Q3_23_NHS_review was removed from gene: COL4A1.
Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: COL4A1 were changed from Walker Warburg Syndrome to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773; autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, MONDO:0012726
Publications for gene: COL4A1 were set to 28056338; 22037604; 21625620
Tag Q3_23_promote_green tag was added to gene: COL4A1. Tag Q3_23_NHS_review tag was added to gene: COL4A1.
gene: COL4A1 was added gene: COL4A1 was added to Congenital muscular dystrophy and congenital myopathy. Sources: NHS GMS,Expert Review Amber,London South GLH,Expert Review Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: COL4A1 were set to 28056338; 22037604; 21625620 Phenotypes for gene: COL4A1 were set to Walker Warburg Syndrome Penetrance for gene: COL4A1 were set to Complete