Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: POMK

Comment on list classification: This gene will remain Red based on the overall reviews and comments from reviewers.

Created: 28 Nov 2019, 5:33 p.m. | Last Modified: 28 Nov 2019, 5:33 p.m.

Panel Version: 1.184

Red List (low evidence)

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), autosomal recessive disorder with congenital muscular dystrophy

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

Panel Version: 1.97

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Limb-girdle muscular dystrophy

Publications

• 24925318

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

More evidence needed. PubMed: 24925318 - 2 sibs, born of consanguineous Jordanian parents, with a homozygous truncating mutation in the POMK gene (Q109X). The mutation was found by homozygosity mapping followed by candidate gene sequencing. Morpholino knockdown of the pomk gene in zebrafish embryos resulted in a small head, delayed ocular development, shortened thicker tail, U-shaped somites, motility defects, and increased mortality. Analysis of the tail muscle showed dystrophic features and decreased DAG1 glycosylation. PubMed: 29910097 compound heterozygous mutations causing limb-girdle muscular dystrophy-dystroglycanopathy in a sib pair (1 variant quite a bit of MAF).

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, 616094; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249

Publications

• 24925318
• 29910097

Given the spectrum of neuromuscular phenotypes associated with this gene there is justification for including this in this panel

Created: 29 Mar 2019, 1:53 p.m.

Phenotypes
limb girdle musuclar dystorphy; congenital muscular dystrophy

Publications

• PMID: 24925318

Comment when marking as ready: Associated with phenotype in OMIM, not G2P. Found in 1/4 sources. One Expert reviewer recommends Amber. One variant (c.325C>T, p.Q109*) has been identified in consanguineous Jordanian twins with Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, (OMIM 616094). This variant has also been reported in consanguineous siblings (ethnicity not reported) with Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 (OMIM 615249).
Emma Clement comments: insufficient evidence under the strongest criteria to make this green, due to lack of numbers. However, based on the behaviour of the other genes in this pathway you would expect this gene to produce CMD and LGMD phenotypes.

Created: 9 Jun 2016, 2:41 p.m.

Comment on list classification: Good evidence in more severe forms; less clear how commonly this gene causes LGMD phenotype.

Created: 29 May 2016, 7:41 p.m.