Syndromic Retinopathy

Gene: TREX1

Green List (high evidence)

Retinal vasculopathy with cerebral leukodystrophy is an adult-onset autosomal dominant disorder involving the microvessels of the brain and resulting in central nervous system degeneration with progressive loss of vision, stroke, motor impairment, and cognitive decline. A subset of affected individuals have systemic vascular involvement evidenced by Raynaud's phenomenon, micronodular cirrhosis, and glomerular dysfunction.

Variants cluster at the C terminus of the TREX1 gene.

Created: 15 Oct 2020, 2:43 a.m. | Last Modified: 15 Oct 2020, 2:43 a.m.

Panel Version: 0.137

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Vasculopathy, retinal, with cerebral leukodystrophy, MIM# 192315

Publications

• 17660820

Green List (high evidence)

*AD Aicardi-Goutieres syndrome caused by a single missense - p.D200N - dominant negative mechanism
*AR Aicardi-Goutieres syndrome, systemic lupus erythematosus - loss of function mechanism (variants impair the enzyme activity of the protein (PMID: 21937424))
*Chilblain lupus caused by a single missense - p.D18N - dominant negative mechanism
*Retinal Vasculopathy with Cerebral Leukodystrophy caused by heterozygous C-terminal frameshifts resulting in truncated proteins that retain exonuclease activity but lose normal perinuclear localization (OMIM)

Created: 19 Feb 2020, 2:03 a.m. | Last Modified: 19 Feb 2020, 2:03 a.m.

Panel Version: 0.1386

Phenotypes
Aicardi-Goutieres syndrome 1, dominant and recessive; Chilblain lupus; {Systemic lupus erythematosus, susceptibility to}; Vasculopathy, retinal, with cerebral leukodystrophy

Publications

• 21937424

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice