Congenital muscular dystrophy and congenital myopathy

Gene: GOLGA2

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)

Comment on list classification: As reviewed by Hannah Knight, there are three unrelated cases and zebrafish model in support of the disease association. Hence, this gene can be promoted to green rating in the next GMS review.

Created: 21 Dec 2023, 8:56 p.m. | Last Modified: 21 Dec 2023, 8:56 p.m.

Panel Version: 0.201

Hannah Knight (NIHR BioResource - University of Cambridge) reviewing this gene on the old GMS Congenital muscular dystrophy panel on 16 Nov 2023 notes (rated Green): 'PMID: 34424553 report a third family with this disorder, presenting with microcephaly, seizures, and myopathy. A novel homozygous stop gain variant was identified'.

Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal

Phenotypes: Developmental delay with hypotonia, myopathy, and brain abnormalities

Publications: 34424553

Created: 21 Dec 2023, 8:55 p.m. | Last Modified: 21 Dec 2023, 8:55 p.m.

Panel Version: 0.200

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Developmental delay with hypotonia, myopathy, and brain abnormalities, OMIM:620240

Publications

• 34424553

Comment on list classification: Promoted from red to amber. GOLGA2 is not associated with any phenotype on OMIM or Gene2Phenotype. As the case presented in PMID: 30237576 lacked any information about patient family history, it is unclear whether the variant tracks with the phenotype. Therefore, given this gene an amber rating until further evidence is available.

Created: 6 Aug 2019, 10:34 a.m. | Last Modified: 6 Aug 2019, 10:34 a.m.

Panel Version: 1.51

Comment on publications: PMID: 26742501 reported on a consanguineous Saudi family where the proband is diagnosed with a neuromuscular disorder characterized by developmental delay, seizures, microcephaly and muscular dystrophy. The proband is homozygous for a small deletion in the GOLGA2 gene which resulted in a frameshift mutation. The same researchers knocked down zebrafish golga2 and showed that this affected the skeletal muscles of the fish and recapitulated the human phenotype.

PMID: 30237576 is a large, high-throughput Mendelian disease study. One patient with global developmental delay, microcephaly and motor weakness affecting lower extremities. Muscle biopsy showed muscular dystrophy. The patient is homozygous for a different small deletion variant that causes frameshift mutation. No other details are given about family history/pedigree.

Created: 6 Aug 2019, 10:27 a.m. | Last Modified: 6 Aug 2019, 10:27 a.m.

Panel Version: 1.50

I don't know

After review with Genomics England clinical team this gene was provisionally rated Amber on the basis of one family, as it is difficult to be confident about the extent of the phenotype so amber pending further cases or expert opinion.

Created: 14 Oct 2019, 12:51 p.m. | Last Modified: 14 Oct 2019, 12:51 p.m.

Panel Version: 1.63

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
secondary dystroglycanopathy

Variants in this GENE are reported as part of current diagnostic practice