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- Title
Linking Genetic Duplications to Choroideremia Pathology.
- Authors
Chi, Jonathan Y.; MacDonald, Ian M.; Hume, Stacey
- Abstract
Introduction. Choroideremia is an X-linked progressive chorioretinal degenerative disease that affects 1 in 50,000 males. Clinically, patients with choroideremia present with nightblindness and progressive loss of peripheral vision; however, typically central vision and colour vision is maintained. Choroideremia arises from a dysfunctional Rab escort protein-1 (REP-1) which is encoded by the CHM gene. The absence of REP-1 in the eye, results in the gradual degeneration of the retina, retinal pigment epithelium, and choroid causing the ocular manifestations common in affected individuals. The exact pathogenesis, however, has yet to be determined. Through genetic studies, we have determined that choroideremia can arise from deletions in the CHM gene but deletions alone do not account for all cases of choroideremia. Our study delves into the biochemical genetics of the CHM gene to determine whether other genetic mutations such as copy number variants play a role in choroideremia pathogenesis. Methods. We designed a multiplex ligation-dependent probe amplification (MLPA) assay kit for the detection of copy number variants in the CHM gene. Using our MLPA assay kit, we tested the DNA of several choroideremia patients that screened negative for genetic deletions in their CHM gene. Results. A duplication of several consecutive exons of the CHM gene was determined in one particular patient DNA sample. Discussion. Prior to this study, only deletions in the CHM gene have been linked to choroideremia pathology. The duplication in the CHM gene observed in this study represents a novel pathological mutation and potentially a novel mechanism of pathogenesis. We hope that this discovery will help us further understand the pathogenesis of choroideremia.
- Subjects
DEGENERATION (Pathology); VITAMIN A; BIOCHEMICAL genetics; PERIPHERAL vision; BLINDNESS; VISION disorders
- Publication
UBC Medical Journal, 2011, Vol 2, Issue 2, p50
- ISSN
1920-7425
- Publication type
Abstract