simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss a multicenter study同时检测多个突变的入侵者检测提高了分子诊断遗传性听力损失的多中心研究.pdfVIP

Simultaneous Screening of Multiple Mutations by Invader Assay Improves Molecular Diagnosis of Hereditary Hearing Loss: A Multicenter Study 1 1 2 2 2 Shin-ichi Usami *, Shin-ya Nishio , Makoto Nagano , Satoko Abe , Toshikazu Yamaguchi , the Deafness Gene Study Consortium 1 Department of Otorhinolaryngology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan, 2 Department of Clinical Genomics, Biomedical Laboratories, Inc., Matoba, Kawagoe-shi, Saitama, Japan 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