Congenital muscular dystrophy

Gene: COL4A1

I don't know

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Insufficient evidence for CMD, however decision may be different for other panels as been implicated with muscle cramps.

Created: 26 Sep 2024, 1:47 p.m. | Last Modified: 26 Sep 2024, 1:58 p.m.

Panel Version: 4.29

Based on the review published by Rannikmäe et al (PMID: 32842921), numerous COL4A1 variants have been associated with muscle phenotypes (supplementary table IIIA).

Created: 28 Sep 2023, 4:07 p.m. | Last Modified: 28 Sep 2023, 4:07 p.m.

Panel Version: 4.11

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 28 Sep 2023, 4:03 p.m. | Last Modified: 28 Sep 2023, 4:03 p.m.

Panel Version: 4.11

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 32842921

Green List (high evidence)

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.

Created: 16 Jun 2023, 3:34 p.m. | Last Modified: 16 Jun 2023, 3:34 p.m.

Panel Version: 4.9

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 18160688
• 20818663

I don't know

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.

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
walker warburg syndrome, muscle eye brain disease

Publications

• 28056338
• 22037604
• 21625620

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

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

• 21625620

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 cases

Created: 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 cases

Created: 19 Dec 2016, noon

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
walker warburg syndrome, muscle eye brain disease