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Title: A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice.
Authors: Sanchez-Alcudia, Rocio
Garcia-Hoyos, Maria
Lopez-Martinez, Miguel A.
Sanchez-Bolivar, Noelia
Zurita, Olga
Gimenez, Ascension
Villaverde, Cristina
Rodrigues-Jacy da Silva, Luciana
Corton, Marta
Perez-Carro, Raquel
Torriano, Simona
Kalatzis, Vasiliki
Rivolta, Carlo
Avila-Fernandez, Almudena
Lorda, Isabel
Trujillo-Tiebas, Maria J.
Garcia-Sandoval, Blanca
Lopez-Molina, Maria I.
Blanco-Kelly, Fiona
Riveiro-Alvarez, Rosa
Ayuso, Carmen
First Published: 12-Apr-2016
Publisher: Public Library of Science
Citation: PLoS One, 2016, 11 (4): e0151943
Abstract: Choroideremia (CHM) is a rare X-linked disease leading to progressive retinal degeneration resulting in blindness. The disorder is caused by mutations in the CHM gene encoding REP-1 protein, an essential component of the Rab geranylgeranyltransferase (GGTase) complex. In the present study, we evaluated a multi-technique analysis algorithm to describe the mutational spectrum identified in a large cohort of cases and further correlate CHM variants with phenotypic characteristics and biochemical defects of choroideremia patients. Molecular genetic testing led to the characterization of 36 out of 45 unrelated CHM families (80%), allowing the clinical reclassification of four CHM families. Haplotype reconstruction showed independent origins for the recurrent p.Arg293* and p.Lys178Argfs*5 mutations, suggesting the presence of hotspots in CHM, as well as the identification of two different unrelated events involving exon 9 deletion. No certain genotype-phenotype correlation could be established. Furthermore, all the patients´ fibroblasts analyzed presented significantly increased levels of unprenylated Rabs proteins compared to control cells; however, this was not related to the genotype. This research demonstrates the major potential of the algorithm proposed for diagnosis. Our data enhance the importance of establish a differential diagnosis with other retinal dystrophies, supporting the idea of an underestimated prevalence of choroideremia. Moreover, they suggested that the severity of the disorder cannot be exclusively explained by the genotype.
DOI Link: 10.1371/journal.pone.0151943
eISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Genetics

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