Inherited bleeding disorders

Gene: GBA

Green List (high evidence)

GBA (glucosylceramidase beta)
EnsemblGeneIds (GRCh38): ENSG00000177628
EnsemblGeneIds (GRCh37): ENSG00000177628
OMIM: 606463, Gene2Phenotype
GBA is in 23 panels

2 reviews

Kate Downes (Uni of Cambridge / CUH)

Red List (low evidence)

Pathogenic variants in GBA are associated with the recessive disorder Gauchers disease. Gauchers is a lysosome neurodegenerative disorder that causes variable multi organ symptoms, that can include thrombocytopenia. The primary diagnosis of Gauchers disease relies on demonstration of deficient glucocerebrosidase (glucosylceramidase) enzyme activity.

Known pathogenic GBA variants, causing variable symptoms, are rare in most population, however, in the Ashkenazi Jewish population carrier frequency can be 1:18. Therefore, appropriate genetic counselling is necessary prior to testing, particularly in high risk populations, by a specialist clinical care team.

Pastores GM, Hughes DA. Gaucher Disease. 2000 Jul 27 [Updated 2018 Jun 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1269/
Created: 25 Jan 2019, 10:10 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Update from NIHRRD-BR BRIDGE they will no longer be reporting on this gene on their platform. After discussion with Genomics England Clinical team, as the MOI is listed as biallelic we would only prioritise variants that are homozygous or compound het. A parent might be found to be a carrier, when their child has the condition but that is to be expected and would be useful information. Gaucher is associated with haematological manifestations as part of the wider syndromic phenotype.
Created: 12 Nov 2018, 5:17 p.m.
Comment on list classification: New gene from NIHRRD-BR BRIDGE Bleeding and Platelet Disorders project, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green.
Created: 18 Sep 2018, 3:43 p.m.
New bleeding, platelet, coagulation and thrombotic disorder Tier 1 reportable gene from NIHRRD-BR BRIDGE project, announced at ISTH-SSC meeting Dublin 2018.
Sources: Expert list
Created: 18 Sep 2018, 3:43 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Gaucher disease; Gaucher disease, perinatal lethal, 608013; Gaucher disease, type I, 230800; Gaucher disease, type II,230800; Gaucher disease, type III, 230800; Gaucher disease, type IIIC, 231005; Platelet disorder

Publications

History Filter Activity

18 Sep 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: gba has been classified as Green List (High Evidence).

18 Sep 2018, Gel status: 1

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

Louise Daugherty (Genomics England Curator)

gene: GBA was added gene: GBA was added to Inherited bleeding disorders. Sources: Expert list Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GBA were set to 15813845 Phenotypes for gene: GBA were set to Gaucher disease; Gaucher disease, perinatal lethal, 608013; Gaucher disease, type I, 230800; Gaucher disease, type II,230800; Gaucher disease, type III, 230800; Gaucher disease, type IIIC, 231005 Review for gene: GBA was set to GREEN