Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
Gene: POMKComment 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
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), autosomal recessive disorder with congenital muscular dystrophyCreated: 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
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.
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
Given the spectrum of neuromuscular phenotypes associated with this gene there is justification for including this in this panelCreated: 29 Mar 2019, 1:53 p.m.
Phenotypes
limb girdle musuclar dystorphy; congenital muscular dystrophy
Publications
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.
Phenotypes for gene: POMK were changed from ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, 616094; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249; limb girdle muscular dystrophy; congenital muscular dystrophy to ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12 OMIM:616094; limb-girdle muscular dystrophy due to POMK deficiencyMONDO:0014489; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 OMIM:615249; muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 MONDO:0014101
Publications for gene: POMK were set to 24925318; 24556084; 29910097
Gene: pomk has been classified as Red List (Low Evidence).
Source Yorkshire and North East GLH was added to POMK.
Phenotypes for gene: POMK were changed from ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, 616094; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249; mb girdle musuclar dystorphy; congenital muscular dystrophy to ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, 616094; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249; limb girdle muscular dystrophy; congenital muscular dystrophy
Phenotypes for gene: POMK were changed from ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, 616094; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249 to ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, 616094; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249; mb girdle musuclar dystorphy; congenital muscular dystrophy
Publications for gene: POMK were set to 24925318; 24556084
Source NHS GMS was added to POMK.
Source South West GLH was added to POMK.
Comments from Fiona Karet included. A Green review for each gene relevant for this panel on the Gene Advisor download has been included.
Phenotypes for POMK were set to ?Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 12, 616094; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, 615249
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Mode of inheritance for POMK was changed to BIALLELIC, autosomal or pseudoautosomal
Publications for POMK were set to 24925318; 24556084
Publications for POMK were set to 24925318
This gene has been classified as Amber List (Moderate Evidence).
POMK was added to Limb girdle muscular dystrophypanel. Sources: Radboud University Medical Center, Nijmegen