Congenital muscular dystrophy and congenital myopathy

Gene: GGPS1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 4:51 p.m. | Last Modified: 1 Feb 2023, 4:51 p.m.

Panel Version: 3.22

Green List (high evidence)

10 unrelated families reported with muscular dystrophy with/without hearing loss and recessive variants in GGPS1 gene. patients presented a phenotype caractherised by early onset proximal weakness, with a subset of individuals also presenting hearing loss and primary ovarian insufficiency (in postpubertal females). Muscle histology is dystrophic. Functional studies showed delayed membrane healing after laser injury in patient-derived myogenic cells, and a knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality. in view of the supporting evidence, this gene should be upgraded to GREEN.

Created: 10 Nov 2022, 12:24 p.m. | Last Modified: 10 Nov 2022, 12:24 p.m.

Panel Version: 2.31

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
GGPS1-associated muscular dystrophy with and without hearing loss.

Publications

• 35869884
• 32403198

Mode of pathogenicity
Other

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype.

PMID:32403198 all 6 unrelated families are from different ethnic backgrounds and all had missense variants (hom or compound het). All have muscle dystrophy, contractures were noted in the more severe patients (4/11), 10/11 hearing loss, 3/3 affected females have ovariant insufficiency (other 3 females are undetermined due to age), 8/10 failure to thrive/short stature.

There is enough evidence to support a gene-disease association. This gene should be Green at the next review.

Created: 18 Oct 2021, 8:46 a.m. | Last Modified: 18 Oct 2021, 8:46 a.m.

Panel Version: 2.18

Green List (high evidence)

11 individuals from 6 unrelated families reported. In addition to proximal weakness, all but one patient presented with congenital sensorineural hearing loss, and all postpubertal females had primary ovarian insufficiency. Muscle histology was dystrophic, with ultrastructural evidence of autophagic material and large mitochondria in the most severe cases. Knock-in mouse of one of the mutations (Y259C) resulted in prenatal lethality.
Sources: Literature

Created: 8 Jul 2020, 12:42 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy; Deafness; Ovarian insufficiency

Publications

• 32403198

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