Türk toplumunda GJB2 (gap junction beta 2 geni; connexin 26) mutasyonları

Abstract

GJB2 (Gap Junction Beta 2 Gene; Connexin 26) Mutations in the Turkish Population Hearing loss occurs in approximately 1 to 3 of 1000 children and approximately 50% of cases have genetic origin. Affected individuals with no additional findings are referred to as nonsyndromic cases. Of these cases with genetic origin, 70% are nonsyndromic. The most common form of hereditary hearing loss is autosomal recessive nonsyndromic hearing loss. Nonsyndromic hearing loss can be diagnosed in persons coming from multiplex or simplex families. Mutations in GJB2 have been identified in deaf people living in many countries, 35delG being the most common mutation in Caucasoid populations. Although in the etiology of hearing loss are a variety of factors, mutations in one gene, GJB2, which encodes for the protein Connexin 26, account for up to 50% of cases of nonsyndromic sensorineural hearing loss in some populations. Here, we present our data about the genetic causes of cases with hearing loss in the Turkish population. Our study group included 358 probands with nonsyndromic hearing loss, in which the age range was between 2-33 years. Of these, 190 cases were multiplex and 168 were simplex. We found 51 probands (14,2%) in homozygous state and 26 probands (7,3%) in heterozygous state for the 35delG mutation. 281 probands (78,5%) were found to be negative for this mutation. Moreover, 10 probands were found to carry the W24X, T55N, 167delT, 299-300delAT, 333-334delAA, 236_239delTGCAinsAGATCCG, delE120, R143W and Y155X mutations as a compound heterozygous mutation with 35delG. 16 probands were found to carry no mutations in the GJB2 coding region. In multiplex cases, mutation screening was performed by PCR-SSCP techniques and probands having band differentiation were analysed using DNA sequencing. As a result, the V27I, El 14G polymorphisms and the delE120 mutation were observed. In our population, mutations in GJB2 present a pattern similar to the distribution of the GJB2 mutations in different countries of Europe. Showing historical relationship with Eastern Asia, polymorphisms belonging to Asian populations were found to be prevalent in our population. The discovery of mutations in GJB2 for the cause of congenital hearing loss will be useful for the early diagnosis and intervention of hearing loss. Key Words: Connexin 26, gap junction, GJB2 gene, hearing loss, Turkish population, 35 delG mutation.