Prevalence of GJB2 causing recessive profound non-syndromic deafness in Japanese children Chieri Hayashi a, *, Manabu Funayama b , Yuanzhe Li c , Kazusaku Kamiya a , Atsushi Kawano d , Mamoru Suzuki d , Nobutaka Hattori b,c , Katsuhisa Ikeda a a Department of Otorhinolaryngology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan b Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Japan c Department of Neurology, Juntendo University School of Medicine, Japan d Department of Otorhinolaryngology, Tokyo Medical University School of Medicine, Tokyo, Japan 1. Introduction People with any degree of sensory impairment may encounter problems such as discrimination within the education system or when looking for work, and a reduced life expectancy. Sensori- neural hearing loss (SNHL) is the most common sensory impairment in developed societies [1,2], where one child in 1000 presents at birth with severe or profound deafness [3]. Recent advances in human genetics have indicated that more than half of congenital SNHL cases involve a genetic factor [4]. In 75–80% of genetic cases, SNHL is the result of autosomal recessive inheritance, and both parents have normal hearing [5]. Mutations of GJB2 are the most frequent cause of autosomal recessive non- syndromic deafness. Indeed, previous studies have shown that GJB2 mutations account for up to 50% of non-syndromic deafness cases [6]. Hearing-impaired subjects with biallelic GJB2 mutations range widely but most commonly follow a severe to profound and non-progressive pattern [7–9]. About 100 different GJB2 muta- tions have been reported globally [the Connexin-Deafness homepage: http://davinci.crg.es/deafness/], and these mutations show a relatively high local dependence (founder effect). A high prevalence of c.35delG has been found among Caucasians; c.235delC among Eastern Asians, including Japanese [10–13]; c.167delT among Ashkenazi Jews [14]; p.R143W among certain Africans [15]; and p.W24X among Indians [16,17] and European Gypsies [18–20]. Some recent reports have indicated a genotype- phenotype correlation: children with two truncating mutations, such as c.35delG or c.235delC, are profoundly deaf, while children with a truncating and missense mutation, or two missense mutations, show better hearing [9,21,22]. Since improved speech performance after cochlear implantation in early childhood is usually observed in hearing-impaired subjects with GJB2 muta- tions [23], the genetic testing of newborn babies will provide useful prognostic information when selecting appropriate treat- ment for such children. In the present study, to clarify the frequency and genotype– phenotype correlation of GJB2 mutations in children with profound non-syndromic deafness, we performed genetic testing for GJB2 mutations involving 119 Japanese children who had undergone cochlear implantation with congenital deafness. International Journal of Pediatric Otorhinolaryngology 75 (2011) 211–214 ARTICLE INFO Article history: Received 14 June 2010 Received in revised form 18 October 2010 Accepted 2 November 2010 Available online 26 November 2010 Keywords: Congenital deafness Cochlear implantation Japanese children p.P225L Connexin 26 GJB2 ABSTRACT Objective: GJB2 (gap junction protein, beta 2, 26 kDa: connexin 26) is a gap junction protein gene that has been implicated in many cases of autosomal recessive non-syndromic deafness. Point and deletion mutations in GJB2 are the most frequent cause of non-syndromic deafness across racial groups. To clarify the relation between profound non-syndromic deafness and GJB2 mutation in Japanese children, we performed genetic testing for GJB2. Methods: We conducted mutation screening employing PCR and direct sequencing for GJB2 in 126 children who had undergone cochlear implantation with congenital deafness. Results: We detected 10 mutations, including two unreported mutations (p.R32S and p.P225L) in GJB2. We identified the highest-frequency mutation (c.235delC: 44.8%) and other nonsense or truncating mutations, as in previous studies. However, in our research, p.R143W, which is one of the missense mutations, may also show an important correlation with severe deafness. Conclusion: Our results suggest that the frequencies of mutations in GJB2 and GJB6 deletions differ among cohorts. Thus, our report is an important study of GJB2 in Japanese children with profound non- syndromic deafness. ß 2010 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +81 3 5802 1229; fax: +81 3 5840 7103. E-mail address: chieri-h@juntendo.ac.jp (C. Hayashi). Contents lists available at ScienceDirect International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl 0165-5876/$ – see front matter ß 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2010.11.001