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A novel SVA retrotransposon insertion in the CHM gene results in loss of REP-1 causing choroideremia.
In: Ophthalmic Genetics, Jg. 41 (2020-08-01), Heft 4, S. 341-344
Online
academicJournal
Zugriff:
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. 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). 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. This case is the first report of a SVA insertion in the CHM gene causing choroideremia. [ABSTRACT FROM AUTHOR]
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A novel SVA retrotransposon insertion in the CHM gene results in loss of REP-1 causing choroideremia.
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Autor/in / Beteiligte Person: | Jones, Kaylie D. ; Radziwon, Alina ; Birch, David G. ; MacDonald, Ian M. |
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Zeitschrift: | Ophthalmic Genetics, Jg. 41 (2020-08-01), Heft 4, S. 341-344 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
ISSN: | 1381-6810 (print) |
DOI: | 10.1080/13816810.2020.1768557 |
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