BMC Ear, Nose and Throat Disorders

Background: C.35delG/GJB2 mutation is the most frequent genetic cause of deafness in Caucasians. Another frequent mutation in some Caucasian populations is del(GJB6-D13S1830). Both GJB2 and GJB6 genes belong to the same DFNB1 locus and when the two mutations are found in combination in a hearing-impaired person, a digenic pattern of inheritance is suggested. Methods: We examined 63 Croatian subjects (25 familial and 38 sporadic cases) with prelingual non-syndromic hearing impairment by polymerase chain reaction for the presence of the c.35delG/ GJB2 and the del(GJB6-D13S1830) mutations. Results: Of the 63 unrelated hearing-impaired subjects, the mutation c.35delG/GJB2 was found in 21 subjects (33.3%). In 5 of them the mutation was found in the heterozygous state, all of them being compound heterozygotes, as sequencing revealed a second mutation within the coding region of the gene in 3 subjects, and a splice site mutation in 2 subjects. The del(GJB6-D13S1830) mutation was not found in the investigated hearing-impaired Croatian subjects. Conclusion: Our results contribute to the knowledge of geographic distribution and population genetics of the GJB2 and GJB6 mutations in the Europeans. Background The identification of genes causing non-syndromic hearing impairment has partially resolved the puzzle of clinical and genetic heterogeneity of deafness [1]. Among these genes the gene with the most significant impact on the population genetics and genetic counselling is the GJB2 gene with the mutation c.35delG that accounts for the majority of mutations in deaf Caucasians [1-3]. Studies published so far have reported the differences in frequency of the mutation in different populations, and its variability in clinical impact on hearing impairment [4,5]. However, although the mutations in the GJB2 gene are responsible for up to 69% of autosomal recessive nonsyndromic hearing impairment [2], a problem emerges when patients are identified with only one GJB2 mutant allele. Recently, in the same DFNB1 locus, a 309-kb deletion implicating the GJB6 gene, del(GJB6-D13S1830), has been identified, and was found to be very common in non-syndromic hearing-impaired patients from Spain, France, Israel, the United Kingdom and Brazil, suggesting also a possible GJB2 / GJB6 digenic pattern of inheritance of deafness [6,7]. There are no reports on frequencies of the c.35delG/GJB2 and del(GJB6-D13S1830) mutation in Published: 08 December 2005 BMC Ear, Nose and Throat Disorders 2005, 5:11 doi:10.1186/1472-6815-5-11 Received: 26 September 2005 Accepted: 08 December 2005 This article is available from: http://www.biomedcentral.com/1472-6815/5/11 © 2005 Medica et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.