Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: POGLUT1

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

The comment from the GMS reviewers is as follows:
Over the past 3 years, (when we were looking at a slightly larger gene panel (essentially R82 plus 20 genes)) we have screened more than 1000 patients on R82 and for POGLUT1 have not identified any clinically significant variants.

Created: 5 Dec 2024, 5:12 p.m. | Last Modified: 5 Dec 2024, 5:27 p.m.

Panel Version: 4.40

Green List (high evidence)

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 21 POGLUT1 variants have been reported in at least 20 unrelated cases (PMID: 27807076; 31897643; 33861953). Supportive in vitro and in vivo functional studies were presented in PMID: 31897643.

Created: 28 Feb 2023, 6:07 p.m. | Last Modified: 28 Feb 2023, 6:07 p.m.

Panel Version: 3.9

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

Created: 28 Feb 2023, 5:35 p.m. | Last Modified: 28 Feb 2023, 5:35 p.m.

Panel Version: 3.7

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: 28 Feb 2023, 5:34 p.m. | Last Modified: 28 Feb 2023, 5:34 p.m.

Panel Version: 3.6

Phenotypes
Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232; autosomal recessive limb-girdle muscular dystrophy type 2R1, MONDO:0014977

Publications

• 31897643

Green List (high evidence)

15 patients from 9 unrelated families with novel pathogenic variants.
Unique muscle imaging pattern of “inside-to-outside” fatty degeneration
Onset in childhood or adulthood

Created: 7 Dec 2022, 11:04 a.m. | Last Modified: 7 Dec 2022, 11:04 a.m.

Panel Version: 3.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
limb girdle weakness; thigh weakness; muscle MRI abnormality

Publications

• 31897643

Comment on list classification: Promoted from Red to Amber based on the review and comments from Chiara Marini Bettolo (NUTH), however only one variant has been reported to date.

Created: 28 Nov 2019, 4:29 p.m. | Last Modified: 28 Nov 2019, 4:34 p.m.

Panel Version: 1.127

Green List (high evidence)

new gene added after analysis. Currently provided by HSS for LGMDin Ncl via LGMD panel. Known form of LGMD2Z or LGMDR21

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

Panel Version: 1.97

Sources: Expert list

Created: 10 May 2019, 2:43 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Limb-girdle muscular dystrophy

Publications

• 27807076