Congenital muscular dystrophy and congenital myopathy

Gene: POGLUT1

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 3:45 p.m. | Last Modified: 2 May 2024, 3:45 p.m.

Panel Version: 0.229

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. PMID: 31897643 reports seven POGLUT1 variants in six families with Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232. Supportive in vitro and in vivo functional studies were presented in PMID: 31897643.

Created: 15 Dec 2022, 5:43 p.m. | Last Modified: 15 Dec 2022, 5:43 p.m.

Panel Version: 3.17

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 15 Dec 2022, 5:26 p.m. | Last Modified: 15 Dec 2022, 5:26 p.m.

Panel Version: 3.15

Green List (high evidence)

in addition to adult-onset LGMD R21 (OMIM# 617232), biallelic variants in POGLUT1 gene have been reported in one patient with congenital muscular dystrophy and in two further patients with onset before 3 years of age. The presenting symptom were hypotonia with lower limb proximal weakness after gait acquisition, and further progression with mild weakness, wasting and contractures of the upper limbs, mild facial weakness, ptosis, and nasal voice. weakness was more severe and had faster progression compared to later onset patients. Muscle biopsies show evidence of α-dystroglycan hypoglycosylation. POGLUT1 activity is critical for the Notch signalling pathway, as JAG2. In view of these evidences, this gene should be considered green for CMD panel as well, in addition to LGMD panel.

Created: 10 Nov 2022, 4:02 p.m. | Last Modified: 10 Nov 2022, 4:02 p.m.

Panel Version: 2.31

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
muscular dystrophy, secondary alpha-dystroglycanopathy

Publications

• 33861953

Mode of pathogenicity
Other

Comment on list classification: Promoted from red to amber. POGLUT1 may be associated with LGMD on OMIM but not associated with any phenotype in Gene2Phenotype. PMID: 27807076 reported on a family (Spanish descent) of 4 affected siblings with recessive limb-girdle muscular dystrophy 21 born from consanguineous parents. All affected siblings were homozygous for a missense variant in POGLUT1. The same study also reported on a Drosophila model where the variant affected muscle development. There is currently not enough evidence to support a gene-disease assocation (only 1 reported case and 1 animal model), therefore POGLUT1 has been given amber gene rating until further evidence is available where the gene status can be re-evaluated.

However, this gene may be more appropriate in the LGMD panel (code: 185) instead of this one.

Created: 7 Aug 2019, 9:06 a.m. | Last Modified: 7 Aug 2019, 9:45 a.m.

Panel Version: 1.55

I don't know

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.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Muscular dystrophy, limb-girdle, autosomal recessive 21, 617232

Publications

• 27807076