This report describes retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, a small-vessel disease that affects highly vascularized tissues including the retina, brain, liver, and kidneys. The human gene implicated is TREX1, Three Prime Repair Exonuclease 1. There is one high-scoring fly ortholog, Dmel\CG3165, for which multiple genetic reagents, classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Multiple UAS constructs of the human Hsap\TREX1 gene, including wild-type and variants implicated in human disease, have been introduced into flies. See the 'Disease-Implicated Variants' table below.
Eye-specific expression of wild-type Hsap\TREX1 results in a rough-eye phenotype. This phenotype is more pronounced when C-terminally truncated or enzymatically inactive Hsap\TREX1 is driven in the developing eye. Mutant isoforms of Hsap\TREX1 exhibit a different subcellular localization than wild-type Hsap\TREX1; while wild-type protein is predominantly cytoplasmically localized, the truncated and enzymatically inactive proteins are localized throughout the cell, including a much larger fraction in the cell nucleus.
[updated June 2024 by FlyBase; FBrf0222196]
[VASCULOPATHY, RETINAL, WITH CEREBRAL LEUKOENCEPHALOPATHY AND SYSTEMIC MANIFESTATIONS; RVCLS](https://omim.org/entry/192315)
[3-PRIME REPAIR EXONUCLEASE 1; TREX1](https://omim.org/entry/606609)
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) 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. Death occurs in most patients 5 to 10 years after onset. A subset of affected individuals have systemic vascular involvement evidenced by Raynaud phenomenon, micronodular cirrhosis, and glomerular dysfunction (summary by Richards et al., 2007, pubmed:17660820). [from MIM:192315; 2024.06.12]
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) is caused by heterozygous mutation in the TREX1 gene on chromosome 3p21. [from MIM:192315; 2024.06.12]
TREX1 encodes Three Prime Repair Exonuclease 1, a nuclear protein with 3' exonuclease activity. The encoded protein may play a role in DNA repair and serve as a proofreading function for DNA polymerase. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, Cree encephalitis, and other diseases of the immune system. [provided by RefSeq, Sep 2012]
Two to one (2 human to 1 Drosophila); GRM1 has one high-scoring Drosophila ortholog, CG3165.
High-scoring ortholog of human TREX1, TREX2 (1 Drosophila to 2 human).
