Congenital muscular dystrophy

Gene: GGPS1

Green List (high evidence)

GGPS1 (geranylgeranyl diphosphate synthase 1)
EnsemblGeneIds (GRCh38): ENSG00000152904
EnsemblGeneIds (GRCh37): ENSG00000152904
OMIM: 606982, Gene2Phenotype
GGPS1 is in 4 panels

4 reviews

Eleanor Williams (Genomics England Curator)

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

Anna Sarkozy (Great Ormond Street Hospital)

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

Mode of pathogenicity
Other

Ivone Leong (Genomics England Curator)

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

Zornitza Stark (Australian Genomics)

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

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
Phenotypes
  • Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome, OMIM:619518
OMIM
606982
Clinvar variants
Variants in GGPS1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 Feb 2023, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q4_21_rating was removed from gene: GGPS1.

1 Feb 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source Expert Review Green was added to GGPS1. Source NHS GMS was added to GGPS1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

15 Dec 2022, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: GGPS1 were set to 32403198

18 Oct 2021, Gel status: 2

Added Tag

Ivone Leong (Genomics England Curator)

Tag Q4_21_rating tag was added to gene: GGPS1.

18 Oct 2021, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: ggps1 has been classified as Amber List (Moderate Evidence).

18 Oct 2021, Gel status: 0

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: GGPS1 were changed from Muscular dystrophy; Deafness; Ovarian insufficiency to Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome, OMIM:619518

8 Jul 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: GGPS1 was added gene: GGPS1 was added to Congenital muscular dystrophy. Sources: Literature Mode of inheritance for gene: GGPS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GGPS1 were set to 32403198 Phenotypes for gene: GGPS1 were set to Muscular dystrophy; Deafness; Ovarian insufficiency Review for gene: GGPS1 was set to GREEN gene: GGPS1 was marked as current diagnostic