GENETIC TESTING Volume 10, Number 4, 2006 © Mary Ann Liebert, Inc. DOI: 10.1089/gte.2006.285-289 High Frequency of 35delG GJB2 Mutation and Absence of del(GJB6-D13S1830) in Greek Cypriot Patients with Nonsyndromic Hearing Loss VASSOS NEOCLEOUS, 1 ANDREAS ASPRIS, 2 VASKEN SHAHPENTERIAN, 3 VASSOS NICOLAOU, 3 CHARALAMBOS PANAGI, 4 IOANNIS IOANNOU, 3 YIANNIS KYAMIDES, 2 VIOLETTA ANASTASIADOU, 5,6 and LEONIDAS A. PHYLACTOU 1 ABSTRACT Mutations in the GJB2 (Connexin 26) gene are responsible for more than half of all cases of prelingual, re- cessive, inherited, nonsyndromic deafness in Europe. This paper presents a mutation analysis of the GJB2 and GJB6 (Connexin 30) genes in 30 Greek Cypriot patients with sensorineural nonsyndromic hearing loss compatible with recessive inheritance. Ten of the patients (33.3%) had the 35delG mutation in the GJB2 gene. Moreover, 9 of these were homozygous for the 35delG mutation, whereas 1 patient was in the compound het- erozygous state with the disease causing E47X nonsense mutation. Another patient with severe sensorineural hearing loss was heterozygous for the V153I missense mutation. Finally, no GJB6 mutations or the known del(GJB6-D13S1830) were identified in any of the investigated Greek Cypriot nonsyndromic hearing loss pa- tients.This work confirms that the GJB2 35delG mutation is an important pathogenic mutation for hearing loss in the Greek Cypriot population. This finding will be used toward the effective diagnosis of nonsyndromic hearing loss, improve genetic counseling, and serve as a potential therapeutic platform in the future for the affected patients in Cyprus. 285 INTRODUCTION D EAFNESS IS A FREQUENT DISORDER affecting approximately 1 in 1,000 children, and about 50% of the cases have genetic causes (Petit et al. 2001). Genetic deafness is divided into syndromic (30%) and nonsyndromic (70%) forms (Hereditary Hearing Loss Homepage, http://davinci.crg.es/deafness/). Among hereditary nonsyndromic deafness, autosomal recessive forms ac- count for the majority (75–85%) of the cases. Mutations in the GJB2 gene (Connexin 26) account for about 50% of the reces- sively inherited cases of nonsyndromic deafness (DFNB1) (Denoyelle et al. 1997; Kelsell et al. 1997; Estivill et al. 1998; Kenneson et al. 2002). To date, more than 80 disease-causing mutations in GJB2 have been reported. The most common GJB2 mutation in the Caucasian population in familial and sporadic cases of deafness is a recessive nonsense mutation (35delG) re- sulting in a premature termination of translation. A possible cause of this mutation is slipped mispairing during DNA synthesis (Cooper and Krawczak, 1993; Estivill et al. 1998). The carrier frequency of 35delG is estimated at around 2% in the European population (Gasparini et al. 2000). In Mediterranean populations, a notably higher carrier frequency of the mutation 35delG was detected, with 4% and 3.5% in Italian and Greek populations, re- spectively (Estivill et al. 1998; Antoniadi et al. 1999). Moreover, a recent study from our group showed that in the Greek Cypriot population the 35delG mutation had a carrier frequency of 2.5%, or 1 in 41 hearing individuals (Neocleous et al. 2006). This car- rier frequency is lower than the mean value found in other Mediterranean countries (Lucotte et al. 2001; Lucotte and Di- eterlen, 2005; Neocleous et al. 2006). The GJB6 gene, which encodes connexin 30 (Cx30) along with GJB2 gene, comprises the DFNB1 locus at 13q12. Both 1 Department of Molecular Genetics C. The Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus. 2 Department of Otorhinolaryngology, Makarios III Hospital, 1474 Nicosia, Cyprus. 3 Department of Otorhinolaryngology, Limassol General Hospital, 3304 Limassol, Cyprus. 4 Department of Otorhinolaryngology, Larnaca General Hospital, 6301 Larnaca, Cyprus. 5 Department of Pediatrics, Makarios III Hospital, 1474 Nicosia, Cyprus. 6 Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus.