Familial cerebral small vessel disease

Gene: GLA

Green List (high evidence)

GLA (galactosidase alpha)
EnsemblGeneIds (GRCh38): ENSG00000102393
EnsemblGeneIds (GRCh37): ENSG00000102393
OMIM: 300644, Gene2Phenotype
GLA is in 26 panels

2 reviews

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Numerous variants reported in this phenotype
Created: 4 Jul 2016, 9:33 a.m.
Comment on list classification: Tier 1 gene for Cerebral Small Vessel Disorders in BRIDGE Study
Created: 4 Jul 2016, 9:29 a.m.

Rhea Tan (University of Cambridge)

Green List (high evidence)

Fabry disease is an X-linked metabolic disorder caused by mutations in the GLA gene. Fabry causes both ischaemic and haemorrhagic strokes, of different subtypes - small vessel disease, large vessel disease and cardioembolic (due to Fabry-related cardiac disease). White matter hyperintensities are also common on brain imaging. Other clinical features include acroparaesthesia, pain crises in the extremities, renal failure, gastrointestinal, cardiac, respiratory and orthopaedic involvement. Patient smay have asymptomatic ocular involvement, with tortuous retinal and conjunctival vessels, corneal and lenticular opacities and whorl keratopathy on slit-lamp examination. They may also have reddish-purple angiokeratomas on the skin, first in the periumbilical area, then on the extensor surfaces and mucosal areas. Heterozygous females may not necessarily have mild symptoms. They may also have severe multisystem involvement with life-threatening manifestations. The diagnosis in males can be made by demonstrating low levels of alpha galactosidase enzyme activity in the plasma. Affected females may have normal enzyme levels and thus genetic testing is necessary to confirm a diagnosis.
Created: 23 Jun 2016, 2:21 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Fabry Disease; Cerebral Small Vessel Disease; Stroke; Ischemic Stroke; haemorrhagic stroke

Publications

Details

History Filter Activity

4 Jul 2016, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for GLA were set to Cerebral Small Vessel Disease; Stroke; Ischemic Stroke; haemorrhagic stroke; Fabry disease, Fabry disease, cardiac variant 301500

4 Jul 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

4 Jul 2016, Gel status: 4

Set publications

Sarah Leigh (Genomics England Curator)

Publications for GLA were set to 22037950; 17206462; 15025684

4 Jul 2016, Gel status: 4

Upload gene information

Sarah Leigh (Genomics England Curator)

GLA was added to Familial cerebral small vessel diseasepanel. Sources: Emory Genetics Laboratory,Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN

4 Jul 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

22 Jun 2016, Gel status: 0

Added New Source

Rhea Tan (University of Cambridge)

GLA was added to Familial cerebral small vessel diseasepanel. Sources: Literature

22 Jun 2016, Gel status: 0

Created

Rhea Tan (University of Cambridge)

GLA was created by rheatan