Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: HNRNPDL

Green List (high evidence)

Listed as LGMD D3 on new nomenclature/classification.

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

Panel Version: 1.97

this gene is now listed on the old and new classification for LGMD (LGMD D3)

https://doi.org/10.1016/j.nmd.2018.05.007

Created: 18 Jun 2019, 9:54 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Limb-girdle muscular dystrophy

Publications

• 30055862
• 24647604
• 15367920

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.

Red List (low evidence)

1 case but found in 'asymptomatic' relatives. PubMed: 24647604 - (p.D378N) in the Brazilian family (10 affected and 3 asymptomatic) and (p.D378H) in Uruguayan family (9 affected and 3 asymptomatic)

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

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Muscular dystrophy, limb-girdle, type 1G, 609115

Publications

• 24647604

Green List (high evidence)

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, 1:15 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Limb girdle muscular dystrophy

Publications

• PMID: 24647604
• PMID: 15367920

Removed 'watchlist tag' as this has been made Green.

Created: 28 Nov 2019, 5:21 p.m. | Last Modified: 28 Nov 2019, 5:21 p.m.

Panel Version: 1.167

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

Created: 28 Nov 2019, 5:21 p.m. | Last Modified: 28 Nov 2019, 5:21 p.m.

Panel Version: 1.167

Comment on list classification: Promoted from Amber to Green due to overall majority of Green reviews and clinical comments from GLH representatives. This gene seems to now be deemed a LGMD causative gene.

Created: 28 Nov 2019, 5:20 p.m. | Last Modified: 28 Nov 2019, 5:20 p.m.

Panel Version: 1.166

When the gene is knocked down in zebrafish it causes a myopathic phenotype (same study). No new cases have been reported in the literature since this publication in 2014. As both variants are missense and their function was not directly investigated, and there were several asymptomatic family members with the variant, there does not seem to be enough evidence at this point to make this Green. A 'watchlist' tag was added.

Created: 11 Oct 2018, 2:50 p.m.

PMID: 24647604 - Two families with different heterozygous missense variants reported. The mutations were confirmed using Sanger sequencing in 13 Brazilian (10 affected and 3 asymptomatic) and 12 Uruguayan (9 affected and 3 asymptomatic) members and neither present in 14 non-affected adult members from both families nor in 604 Brazilian controls older than 60. No functional studies of these specific variants were carried out.

Created: 21 May 2018, 5:11 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Muscular dystrophy, limb-girdle, type 1G 609115

Publications

• 24647604