Short Report High prevalence of V37I genetic variant in the connexin-26 (GJB2) gene among non-syndromic hearing-impaired and control Thai individuals D Wattanasirichaigoon a , C Limwongse b,c , C Jariengprasert d , PT Yenchitsomanus c , C Tocharoenthanaphol e , W Thongnoppakhun c , C Thawil d , D Charoenpipop e , T Pho-iam c , S Thongpradit e and P Duggal f a Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, b Department of Medicine, c Department of Research and Development, Faculty of Medicine, Siriraj Hospital, d Department of Otolaryngology, e Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, and f Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA Key words: connexin – genes – mutation – sensorineural hearing loss Corresponding author: Duangrurdee Wattanasirichaigoon, MD, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Bangkok 10400, Thailand. Tel.: þ66 2 201 1244; fax: þ66 2 201 1850; e-mail: radwc@mahidol.ac.th Received 11 April 2004, revised and accepted for publication 14 June 2004 Wattanasirichaigoon D, Limwongse C, Jariengprasert C, Yenchitsomanus PT, Tocharoenthanaphol C, Thongnoppakhun W, Thawil C, Charoenpipop D, Pho-iam T, Thongpradit S, Duggal P. High prevalence of V37I genetic variant in the connexin-26 (GJB2) gene among non-syndromic hearing-impaired and control Thai individuals. Clin Genet 2004: 66: 452–460. # Blackwell Munksgaard, 2004 Hearing loss is highly prevalent with a worldwide incidence of 1–2 per 1000 newborns. Several previous studies have demonstrated that mutationsofconnexin26(Cx26 or GJB2)areresponsibleformostcases of the recessive non-syndromic sensorineural hearing loss (NSSHL). Certain mutations have been described frequently among various populations, which include 35delG, 167delT, and 235delC. Recently, a missense mutation, V37I, was reported as a pathogenic change in East Asian affected individuals. To identify genetic variants associated with NSSHL in Thai population, we performed mutation analysis of Cx26 in 166 unrelated probands with NSSHL and 205 controls. We identified seven novel genetic variants in Cx26. We also identified a high prevalenceoftheV37Imutationamongbothaffectedprobands(11.1%) and control subjects (8.5%), which suggests that the pathologic role of V37Imaybemodifiedbyothergenes.Ourdatasupportpreviousstudies that show heterogeneity in the frequencies and types of mutations in Cx26 within populations and among ethnicities and that before clinical significance and causality can be attributed to a genetic variant, functional characterization is necessary. Molecular genetic studies of deafness have increased tremendously in the past 5years (1, 2). To date, more than 85 loci for non-syndromic sensorineural hearing loss (NSSHL) have been mapped, with 25 genes identified including several gap junction protein encoding genes (3). Gap junctions are intercellular proteins formed by connexins (Cx), which belong to a multigene family (4, 5). Connexins oligomerize to form con- nexon, either a homohexamer or heterohexamer (4, 5). Mutations in human GJB2 (Cx26), GJB6 (Cx30), GJB3 (Cx31), and GJA1 (Cx43) genes have been found to underlie both syndromic and NSSHL (6–11). Disclaimer: The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, or does mention of trade names, commercial products, or organizations imply endorsement by the US government. Clin Genet 2004: 66: 452–460 Copyright # Blackwell Munksgaard 2004 Printed in Denmark. All rights reserved CLINICAL GENETICS doi: 10.1111/j.1399-0004.2004.00325.x 452