%0 Journal Article
%T Evidence for Central Asian Origin of the p.Val27Ile Variant in the GJB2 Gene
%A Guille Garc¨ªa S¨¢nchez
%A Alfonso Alfaro-Rodr¨ªguez
%A Adri¨¢n Poblano
%J International Journal of Medical Genetics
%D 2014
%R 10.1155/2014/856313
%X The mutations in the GJB2 gene are the most common cause of nonsyndromic hearing impairment and they are associated with the population¡¯s ethnic background. The p.Val27Ile is frequent in both Asia and America. In this retrospective study, we report the findings from the GJB2 screening and the audiological exams conducted on 125 Mexican mestizo patients with non-syndromic hearing impairment; they were treated at the Instituto Nacional de Rehabilitacion in Mexico City. The most frequent audiometric findings were bilateral, symmetrical, and profound hearing impairment. The allele frequencies in the GJB2 screening were p.Val27Ile 15%, other mutations 5%, and wild type 80%. We found no correlation between GJB2 genotype and auditory phenotype. The high allele frequency of p.Val27Ile was a very interesting finding. Our research suggests that p.Val27Ile arose in an ancient common ancestor who lived in Altai Republic and then the polymorphism was brought to America by its first inhabitants, the Amerindians. These results enhance our understanding of the peopling of the America, which remains unresolved. 1. Introduction The gap junction ¦Â2 gene (GJB2 [MIM*121011]) (Online Mendelian Inheritance in Man (OMIM), http://www.omim.org/), encoded to the protein connexin 26. Mutations in this gene are the most common cause of hereditary nonsyndromic hearing impairment, causing up to 50% of autosomal recessive cases [1, 2] and up to 37% of unknown cause [3]. Also, although infrequently, mutations in this gene cause genetic syndromes that affect hearing and skin [4, 5]. The frequency of GJB2 variants has been associated with ethnic background. The most frequent pathogenic mutations are c.35delG (p.Gly12ValfsTer1) in Caucasian Europeans [6], c.167delT (p.Leu56ArgfsTer26) in Ashkenazi Jews [7], c.427C>T (p.R143W) in Africans from Ghana [8], c.74G>A (p.W24X) in Indians and Romanies [9, 10], c.109G>A (p.V37Ile) in East Asians [11], and c.235delC (p.L79CfsX3) in East Asians (Japanese, Koreans, and Chinese), Mongolians (Central Asia), and southern Altaians (South Siberia) [12¨C16]. The high carrier frequencies (0.7 to 16%) of each of these pathogenic mutations among the populations in which they are endemic suggest that there may be some evolutionary advantage to being a carrier of these mutations [17]. The most frequent polymorphic variants are c.79G>A (p.Val27Ile) and c.341G>A (p.Glu114Gly); these are most frequent in East Asian populations [12¨C14, 18]. The p.Val27Ile polymorphism has been reported as the most common variant of GJB2 gene in several studies [12¨C16, 18¨C25]. It
%U http://www.hindawi.com/journals/ijmg/2014/856313/