A novel SVA retrotransposon insertion in the CHM gene results in loss of REP-1 causing choroideremia. (3rd July 2020)

• Record Type: Journal Article
• Authors: Jones, Kaylie D.; Radziwon, Alina; Birch, David G.; MacDonald, Ian M.
• Is Part Of: Ophthalmic genetics. Volume 41:Number 4(2020)
• Page Start: 341
• Page End: 344
• Publication Date: 2020-07-03
• Subjects: SVA insertion -- CHM -- REP-1 -- choroideremia -- retrotransposon; Eye -- Diseases -- Genetic aspects -- Periodicals; Eye Diseases -- genetics -- Periodicals; Eye Diseases -- in infancy & childhood -- Periodicals; 617.7
• DOI: 10.1080/13816810.2020.1768557
• Languages: English
• ISSNs: 1381-6810

Abstract

ABSTRACT: Background: Choroideremia is an X-linked retinal disease characterized by progressive atrophy of the choroid and retinal pigment epithelium caused by mutations in the CHM gene. SVA (SINE-R/VNTR/ Alu ) elements are a type of non-autonomous retrotransposon that occasionally self-replicate, reinsert randomly into a gene, and cause disease. Intragenic SVA insertions have been reported as the mechanism underlying a number of diseases including a syndromic form of retinal dystrophy, but have never been found in CHM . Materials and Methods: Here we identified and characterized a novel hemizygous SVA insertion, c.97_98inSVA (p.Arg33insSVA), in exon 2 of CHM in a male choroideremia patient. The SVA insertion's impact was evaluated by establishing a patient-derived lymphoblastoid cell line as a source of RNA for mRNA analysis of the CHM transcript, and protein for immunoblot analysis of Rab Escort Protein 1 (REP-1). Results: Immunoblot analysis revealed the absence of REP-1 protein, while a smaller than expected PCR product was amplified from cDNA. Sequencing of this PCR product showed skipping of exon 2, denoted r.50_116del. Ophthalmic examination including psychophysical tests, visual electrophysiology, and fundus imaging showed the patient's phenotype was consistent with severe early manifestations of choroideremia. Conclusions: This case is the first report of a SVA insertion in the CHM gene causing choroideremia.