title: Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study.
abstract: Although etiological studies have shown genetic disorders to be a common cause of congenital/early-onset sensorineural hearing loss, there have been no detailed multicenter studies based on genetic testing. In the present report, 264 Japanese patients with bilateral sensorineural hearing loss from 33 ENT departments nationwide participated. For these patients, we first applied the Invader assay for screening 47 known mutations of 13 known deafness genes, followed by direct sequencing as necessary. A total of 78 (29.5%) subjects had at least one deafness gene mutation. Mutations were more frequently found in the patients with congenital or early-onset hearing loss, i.e., in those with an awareness age of 0-6 years, mutations were significantly higher (41.8%) than in patients with an older age of awareness (16.0%). Among the 13 genes, mutations in GJB2 and SLC26A4 were mainly found in congenital or early-onset patients, in contrast with mitochondrial mutations (12S rRNA m.1555A>G, tRNA(Leu(UUR)) m.3243A>G), which were predominantly found in older-onset patients. The present method of simultaneous screening of multiple deafness mutations by Invader assay followed by direct sequencing will enable us to detect deafness mutations in an efficient and practical manner for clinical use.
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan. usami@shinshu-u.ac.jp
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Usami
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Nishio
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagano
authors.forename: Satoko
authors.initials: S
authors.lastname: Abe
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D017668:Age of Onset; D043402:Cathepsin A / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D005838:Genotype; D034381:Hearing Loss / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D012335:RNA, Ribosomal / Q000235:genetics; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26; C468629:CTSA protein, human; D043402:Cathepsin A