Congenital muscular dystrophy
Gene: COL4A1
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
Publications
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
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_NHS_review tag was added to gene: COL4A1.
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; 18160688; 20818663
Tag Q3_23_promote_green tag was added to gene: COL4A1.
Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Publications for gene: COL4A1 were set to 28056338; 22037604; 21625620
Phenotypes for gene: COL4A1 were changed from walker warburg syndrome, muscle eye brain disease; Brain small vessel disease with or without ocular anomalies, 175780 to Walker Warburg Syndrome
Phenotypes for gene: COL4A1 were changed from walker warburg syndrome, muscle eye brain disease to walker warburg syndrome, muscle eye brain disease; Brain small vessel disease with or without ocular anomalies, 175780
Source NHS GMS was added to COL4A1.
Source London South GLH was added to COL4A1.
27.01.2017 Panel revised after expert review and internal review with further curation.
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Publications for COL4A1 were set to 28056338;22037604;21625620
This proposed gene was validated and added to this panel
COL4A1 was added to Congenital muscular dystrophypanel. Sources: Expert Review
COL4A1 was created by eclement