Functional analysis of splicing mutations in MYO7A and USH2A genes.
Clin Genet
; 79(3): 282-8, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-20497194
Usher syndrome is defined by the association of sensorineural hearing loss, retinitis pigmentosa and variable vestibular dysfunction. Many disease-causative mutations have been identified in MYO7A and USH2A genes, which play a major role in Usher syndrome type I and type II, respectively. The pathogenic nature of mutations that lead to premature stop codons is not questioned; nevertheless, additional studies are needed to verify the pathogenicity of some changes such as those putatively involved in the splice process. Five putative splice-site variants were detected in our cohort of patients: c.2283-1G>T and c.5856G>A in MYO7A and c.1841-2A>G, c.2167+5G>A and c.5298+1G>C in the USH2A gene. In this study, we analyze these changes with bioinformatic tools and investigate the expression of MYO7A and USH2A transcripts through hybrid minigene assays. Our study showed that all five mutations abolished the consensus splice site producing the skipping of involved exons. In addition, for variant c.2167+5G>A, a new donor splice site was observed. Our data reveal the pathogenic nature of the analyzed variants. The fact that splicing mutations led to in-frame or out-of-frame alterations cannot explain phenotypic differences, thus, genotype-phenotype correlations cannot be inferred.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Splicing de RNA
/
Proteínas da Matriz Extracelular
/
Miosinas
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
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Humans
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Male
Idioma:
En
Revista:
Clin Genet
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Espanha
País de publicação:
Dinamarca