Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: DAG1

Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype.

Created: 28 Nov 2019, 5:11 p.m. | Last Modified: 28 Nov 2019, 5:11 p.m.

Panel Version: 1.157

Comment on list classification: Promoted from Red to Green due to overall reviews and clinical comments from GLH representatives.

Created: 28 Nov 2019, 5:10 p.m. | Last Modified: 28 Nov 2019, 5:10 p.m.

Panel Version: 1.156

Green List (high evidence)

Known form of LGMD2P or LGMDR16

Created: 21 Oct 2019, 1:27 p.m. | Last Modified: 21 Oct 2019, 1:27 p.m.

Panel Version: 1.97

Phenotypes
Limb-girdle muscular dystrophy

Publications

• 14678799
• 21388311
• 30055862

I don't know

Review and rating from Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 30 Apr 2019, 11:45 a.m.

I don't know

PubMed: 25503980 - 7-year-old Japanese boy with a very mild form of MDDGC9 presenting only as asymptomatic increased serum creatine kinase. Identified compound heterozygous missense mutations by WES. In vitro functional expression studies indicated that the mutations did not influence expression of dystroglycan, but did cause a defect in posttranslational modification. One variant is 0.013% (including 1 homoz) and other 0.2% (603 alleles including 1 homoz) in gnomAD - probably too common. PMID: 29036200 - some functional evidence for missense variants identified in paper above but considering MAF this should be used with caution. PubMed: 21388311 - mice with a homozygous T190M mutation in the Dag1 gene, which corresponds to the human T192M mutation, developed muscular dystrophy and neurologic motor impairment. Homoz vlimb-girdle muscular dystrophy-dystroglycanopathy and cognitive impairmentariant, absent from gnomAD and in patient with

Created: 30 Apr 2019, 11:24 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818

Publications

• 25503980
• 29036200
• 21388311

Note that an international expert review of the LGMD genes and nomenclature deemed that this is an LGMD causative gene (PMID: 30055862), I therefore strongly feel that this should be included in this panel list

Created: 29 Mar 2019, 1:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Limb girdle muscular dystrophy; congenital muscular dystrophy

Publications

• PMID: 14678799
• PMID: 21388311

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

Green List (high evidence)

Listed as associated with Limb Girdle Muscular Dystrophy by Gene Advisor (June 2016), Steve Abbs

Created: 27 Jul 2016, 8:21 a.m.

Comment on phenotypes: Also associated with Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9, 616538

Created: 26 Jul 2016, 2:08 p.m.

Comment when marking as ready: Associated with phenotype in OMIM and G2P. Found in 2/4 sources. Expert reviewer recommends Amber. There are a total of three variants reported (could not find any more in the literature), one is found as a homozygote and the other two as compound heterozygotes in one patient. Functional studies done on the latter two variants.
Comment from Emma Clement: probably not sufficient evidence for green status (yet) although feel that very likely to be more LGMD mutations reported in this gene . Pains me to leave it orange as this is a really interesting gene. We searched for ages (research) for mutations in this gene, never found one, hopefully exome will turn up more.
appear to be rare.

Created: 9 Jun 2016, 12:39 p.m.

Comment on mode of inheritance: One patient reported as homozygous for one variant and another reported as a compound heterozygous for two additional variants

Created: 9 Jun 2016, 10:12 a.m.

Comment on list classification: Definitely causes a more severe muscular dystrophy; evidence for LGMD phenotype less convincing.

Created: 29 May 2016, 3:31 p.m.