title: Carrier frequency of the GJB2 mutations that cause hereditary hearing loss in the Japanese population.
abstract: Hearing impairment is one of the most common sensory disorders that affect ~1 in 1000 children, and half of them are considered to be hereditary. Information about the carrier frequencies of mutations that underlie autosomal recessive disorders is indispensable for accurate genetic counseling to predict the probability of patients' children's disease. However, there have been few reports specific to the Japanese population. GJB2 mutations are reported to be the most frequent cause of hereditary hearing loss, and the mutation spectrum and frequency of GJB2 mutations were reported to vary among different ethnic groups. In this study, we investigated the carrier frequency of GJB2 mutations and the mutation spectrum in 509 individuals randomly selected from the general Japanese population. We show that the carrier frequencies of the two most common pathogenic mutations are 1.57% (8/509) for c.235delC and 1.77% (9/509) for p.Val37Ile. In addition to these mutations, we found two pathogenic variants (p.[Gly45Glu;Tyr136*] and p.Arg143Trp), and the total carrier frequency was estimated to be around 3.73% (19/509). We also detected six unclassified variants, including two novel variants (p.Cys60Tyr and p.Phe106Leu), with the former predicted to be pathogenic. These findings will provide indispensable information for genetic counseling in the Japanese population.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Mirei
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.affiliation: Department of Public Health, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nishio
authors.affiliation: Department of Medical Ethics/Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kosugi
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Usami
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kitajiri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26