Familial cerebral small vessel disease

Gene: COL4A1

Comment when marking as ready: Associated with phenotype in G2P. Numerous variants reported in this phenotype.

Created: 1 Jul 2016, 5:23 p.m.

Comment on list classification: Tier 1 gene for Cerebral Small Vessel Disorders in BRIDGE Study

Created: 1 Jul 2016, 5:21 p.m.

Green List (high evidence)

Mutations in COL4A1 and COL4A2 are associated with a spectrum of conditions with both infantile and adult onset, previously described as separate conditions - autosomal dominant Type I Porencephaly, cerebral small vessel disease with haemorrhage, cerebral small vessel disease with Axenfeld-Rieger Anomaly, and Hereditary Angiopathy with Nephropathy, Aneurysms and muscle Cramps (HANAC syndrome).

Type IV collagen is an integral component for basement membranes. Missense mutations, often those resulting in the substitution of a glycine residue, alters the three-dimensional conformation of the alpha-1 chain inhibiting the formation and deposition of collagen heterotrimers in the basement membrane.

Created: 22 Jun 2016, 11:39 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cerebral Small Vessel Disease; stroke; migraine; intracerebral haemorrhage; Axenfeld-Rieger Anomaly; cognitive impairment; dementia; seizures; myopathy; infantile hemiparesis; developmental delay

Publications

• PMID: 21157337
• 17696175
• 16107487
• 19949034
• 1737982
• 17938367