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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2011

Open Access 01-12-2011 | Research

Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations

Authors: Gema Garcia-Garcia, Maria J Aparisi, Teresa Jaijo, Regina Rodrigo, Ana M Leon, Almudena Avila-Fernandez, Fiona Blanco-Kelly, Sara Bernal, Rafael Navarro, Manuel Diaz-Llopis, Montserrat Baiget, Carmen Ayuso, Jose M Millan, Elena Aller

Published in: Orphanet Journal of Rare Diseases | Issue 1/2011

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Abstract

Background

Usher Syndrome type II (USH2) is an autosomal recessive disorder, characterized by moderate to severe hearing impairment and retinitis pigmentosa (RP). Among the three genes implicated, mutations in the USH2A gene account for 74-90% of the USH2 cases.

Methods

To identify the genetic cause of the disease and determine the frequency of USH2A mutations in a cohort of 88 unrelated USH Spanish patients, we carried out a mutation screening of the 72 coding exons of this gene by direct sequencing. Moreover, we performed functional minigene studies for those changes that were predicted to affect splicing.

Results

As a result, a total of 144 DNA sequence variants were identified. Based upon previous studies, allele frequencies, segregation analysis, bioinformatics' predictions and in vitro experiments, 37 variants (23 of them novel) were classified as pathogenic mutations.

Conclusions

This report provide a wide spectrum of USH2A mutations and clinical features, including atypical Usher syndrome phenotypes resembling Usher syndrome type I. Considering only the patients clearly diagnosed with Usher syndrome type II, and results obtained in this and previous studies, we can state that mutations in USH2A are responsible for 76.1% of USH2 disease in patients of Spanish origin.
Appendix
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Metadata
Title
Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations
Authors
Gema Garcia-Garcia
Maria J Aparisi
Teresa Jaijo
Regina Rodrigo
Ana M Leon
Almudena Avila-Fernandez
Fiona Blanco-Kelly
Sara Bernal
Rafael Navarro
Manuel Diaz-Llopis
Montserrat Baiget
Carmen Ayuso
Jose M Millan
Elena Aller
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2011
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-6-65

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