title: Frequency of Usher syndrome type 1 in deaf children by massively parallel DNA sequencing.
abstract: Usher syndrome type 1 (USH1) is the most severe of the three USH subtypes due to its profound hearing loss, absent vestibular response and retinitis pigmentosa appearing at a prepubescent age. Six causative genes have been identified for USH1, making early diagnosis and therapy possible through DNA testing. Targeted exon sequencing of selected genes using massively parallel DNA sequencing (MPS) technology enables clinicians to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using MPS along with direct sequence analysis, we screened 227 unrelated non-syndromic deaf children and detected recessive mutations in USH1 causative genes in five patients (2.2%): three patients harbored MYO7A mutations and one each carried CDH23 or PCDH15 mutations. As indicated by an earlier genotype-phenotype correlation study of the CDH23 and PCDH15 genes, we considered the latter two patients to have USH1. Based on clinical findings, it was also highly likely that one patient with MYO7A mutations possessed USH1 due to a late onset age of walking. This first report describing the frequency (1.3-2.2%) of USH1 among non-syndromic deaf children highlights the importance of comprehensive genetic testing for early disease diagnosis.
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Hidekane
authors.initials: H
authors.lastname: Yoshimura
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.|Department of Hearing Implant Science, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Miyagawa
authors.affiliation: Department of Otolaryngology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kumakawa
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.|Department of Hearing Implant Science, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Nishio
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Usami
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012042:Registries; D052245:Usher Syndromes / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*