Primary ovarian insufficiency

Gene: GGPS1

Comment on list classification: Promoted from Amber to Green according to my previous review.

Created: 18 Oct 2021, 8:54 a.m. | Last Modified: 18 Oct 2021, 8:54 a.m.

Panel Version: 1.51

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 has been given a Green rating.

Created: 18 Oct 2021, 8:46 a.m. | Last Modified: 18 Oct 2021, 8:53 a.m.

Panel Version: 1.50

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