NDLI: A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice

Content Provider	PubMed Central
Author	Rocio, Sanchez-alcudia Maria, Garcia-hoyos Lopez-martinez, Miguel Angel Sanchez-bolivar, Noelia Zurita, Olga Gimenez, Ascension Villaverde, Cristina Silva, Luciana Rodrigues-jacy Da Corton, Marta Raquel, Perez-carro Simona, Torriano Kalatzis, Vasiliki Rivolta, Carlo Avila-fernandez, Almudena Lorda, Isabel Trujillo-tiebas, Maria J. Blanca, Garcia-sandoval Isabel, Lopez-molina Maria Fiona, Blanco-kelly Rosa, Riveiro-alvarez Ayuso, Carmen
Editor	Janecke, Andreas R.
Copyright Year	2016
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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0151943
Starting Page	151943
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	4
Volume Number	11
Language	English
Publisher	Public Library of Science
Publisher Date	2016-04-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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