Familial cerebral small vessel disease

Gene: TREX1

Comment when marking as ready: Associated with phenotype in G2P. 3 variants reported in this phenotype

Created: 4 Jul 2016, 2:44 p.m.

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

Created: 4 Jul 2016, 2:43 p.m.

Green List (high evidence)

Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL) is an autosomal dominant form of cerebral small vessel disease, previously described as different overlapping syndromes: cerebroretinal vasculopathy (CRV), hereditary endothelopathy, retinopathy, nephropathy and stroke (HERNS) and hereditary vascular retinopathy (HVR).

Frameshift mutations in the carboxyl-terminus of the TREX1 gene have been reported to cause RVCL. These mutations lead to a truncated C-terminus of DNAse III, leading to cellular mislocalization (rather than loss of activity) of the enzyme.

Loss-of-function mutations in TREX1 which decrease DNAse III enzyme activity have also been reported to be associated with the disease.

Created: 22 Jun 2016, 3:25 p.m.

Cerebral small vessel disease; Aicardi-Goutières syndrome; retinal vasculopathy with cerebral leukodystrophy; cerebroretinal vasculopathy; hereditary endotheliopathy, retinopathy, nephropathy and stroke; stroke, hereditary vascular retinopathy; retinopathy; nephropathy

Created: 22 Jun 2016, 3:25 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
retinal vasculopathy with cerebral leukodystrophy; cerebroretinal vasculopathy; hereditary endotheliopathy, retinopathy, nephropathy and stroke; stroke, hereditary vascular retinopathy; retinopathy; nephropathy

Publications

• PMID:18204807
• 12525718
• 17660820
• 23881107
• 16845398