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

Orphanet Journal of Rare Diseases

Elena Aller²  Jose M Millan⁵  Carmen Ayuso¹  Montserrat Baiget³  Manuel Diaz-Llopis⁶  Rafael Navarro⁷  Sara Bernal³  Fiona Blanco-Kelly¹  Almudena Avila-Fernandez¹  Ana M Leon²  Regina Rodrigo⁴  Teresa Jaijo²  Maria J Aparisi⁴  Gema Garcia-Garcia⁴ 

[1] Servicio de Genética, Fundación Jiménez Díaz, Madrid, Spain;CIBER de Enfermedades Raras (CIBERER), Valencia, Spain;Servei de Genètica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;Grupo de Investigación en Enfermedades Neurosensoriales. Instituto de Investigación Sanitaria IIS-La Fe, Valencia, Spain;Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe, Valencia, Spain;Servicio de Oftalmología, Hospital Universitario La Fe, Valencia, Spain;Instituto de Microcirugía Ocular, Barcelona, Spain

关键词: Sequence Variants;    Mutations;    USH2A;    Usher Syndrome;   

Others  :  866813
DOI  :  10.1186/1750-1172-6-65

 received in 2011-04-04, accepted in 2011-10-17,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Garcia-Garcia et al; licensee BioMed Central Ltd.

【 图 表 】

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