Familial cerebral small vessel disease

Gene: TREX1

Green List (high evidence)

TREX1 (three prime repair exonuclease 1)
EnsemblGeneIds (GRCh38): ENSG00000213689
EnsemblGeneIds (GRCh37): ENSG00000213689
OMIM: 606609, Gene2Phenotype
TREX1 is in 23 panels

2 reviews

Sarah Leigh (Genomics England Curator)

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.

Rhea Tan (University of Cambridge)

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

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • retinal vasculopathy with cerebral leukodystrophy
  • cerebroretinal vasculopathy
  • hereditary endotheliopathy, retinopathy, nephropathy and stroke
  • stroke, hereditary vascular retinopathy
  • retinopathy
  • nephropathy
  • Aicardi-Goutieres syndrome 1, dominant and recessive 225750 AR, AD
  • Vasculopathy, retinal, with cerebral leukodystrophy 192315 AD
OMIM
606609
Clinvar variants
Variants in TREX1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

4 Jul 2016, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for TREX1 were set to retinal vasculopathy with cerebral leukodystrophy; cerebroretinal vasculopathy; hereditary endotheliopathy, retinopathy, nephropathy and stroke; stroke, hereditary vascular retinopathy; retinopathy; nephropathy; Aicardi-Goutieres syndrome 1, dominant and recessive 225750 AR, AD; Vasculopathy, retinal, with cerebral leukodystrophy 192315 AD

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

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: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for TREX1 were set to retinal vasculopathy with cerebral leukodystrophy; cerebroretinal vasculopathy; hereditary endotheliopathy, retinopathy, nephropathy and stroke; stroke, hereditary vascular retinopathy; retinopathy; nephropathy; Aicardi-Goutieres syndrome 1, dominant and recessive 225750 AR, AD; Vasculopathy, retinal, with cerebral leukodystrophy 192315 AD

4 Jul 2016, Gel status: 0

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for TREX1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

4 Jul 2016, Gel status: 0

Set publications

Sarah Leigh (Genomics England Curator)

Publications for TREX1 were set to 18204807; 12525718; 17660820; 23881107; 16845398

4 Jul 2016, Gel status: 0

Upload gene information

Sarah Leigh (Genomics England Curator)

TREX1 was added to Familial cerebral small vessel diseasepanel. Sources: Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN

22 Jun 2016, Gel status: 0

Added New Source

Rhea Tan (University of Cambridge)

TREX1 was added to Familial cerebral small vessel diseasepanel. Sources: Literature

22 Jun 2016, Gel status: 0

Created

Rhea Tan (University of Cambridge)

TREX1 was created by rheatan