Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations
Por:
Garcia-Garcia, G, Aparisi, MJ, Jaijo, T, Rodrigo, R, Leon, AM, Avila-Fernandez, A, Blanco-Kelly, F, Bernal, S, Navarro, R, Diaz-Llopis, M, Baiget, M, Ayuso, C, Millan, JM, Aller, E
Publicada:
17 oct 2011
Resumen:
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.
Filiaciones:
Garcia-Garcia, G:
Inst Invest Sanitaria IIS La Fe, Grp Invest Enfermedades Neurosensoriales, Valencia, Spain
Aparisi, MJ:
Inst Invest Sanitaria IIS La Fe, Grp Invest Enfermedades Neurosensoriales, Valencia, Spain
Jaijo, T:
Inst Invest Sanitaria IIS La Fe, Grp Invest Enfermedades Neurosensoriales, Valencia, Spain
CIBER Enfermedades Raras CIBERER, Valencia, Spain
Rodrigo, R:
Inst Invest Sanitaria IIS La Fe, Grp Invest Enfermedades Neurosensoriales, Valencia, Spain
Leon, AM:
CIBER Enfermedades Raras CIBERER, Valencia, Spain
Avila-Fernandez, A:
CIBER Enfermedades Raras CIBERER, Valencia, Spain
Fdn Jimenez Diaz, Serv Genet, E-28040 Madrid, Spain
Blanco-Kelly, F:
Fdn Jimenez Diaz, Serv Genet, E-28040 Madrid, Spain
Bernal, S:
CIBER Enfermedades Raras CIBERER, Valencia, Spain
Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona, Spain
Navarro, R:
Inst Microcirugia Ocular, Barcelona, Spain
Diaz-Llopis, M:
Hosp Univ La Fe, Serv Oftalmol, Valencia, Spain
Baiget, M:
CIBER Enfermedades Raras CIBERER, Valencia, Spain
Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona, Spain
Ayuso, C:
CIBER Enfermedades Raras CIBERER, Valencia, Spain
Fdn Jimenez Diaz, Serv Genet, E-28040 Madrid, Spain
Millan, JM:
Inst Invest Sanitaria IIS La Fe, Grp Invest Enfermedades Neurosensoriales, Valencia, Spain
CIBER Enfermedades Raras CIBERER, Valencia, Spain
Hosp Univ La Fe, Unidad Genet & Diagnost Prenatal, Valencia, Spain
Aller, E:
Inst Invest Sanitaria IIS La Fe, Grp Invest Enfermedades Neurosensoriales, Valencia, Spain
CIBER Enfermedades Raras CIBERER, Valencia, Spain
Gold, Green Published
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