title: Frequencies of gap- and tight-junction mutations in Turkish families with autosomal-recessive non-syndromic hearing loss.
abstract: Mutations in genes encoding gap- and tight-junction proteins have been shown to cause distinct forms of hearing loss. We have now determined the GJB2[connexin 26 (Cx26)] mutation spectrum in 60 index patients from mostly large Turkish families with autosomal-recessive inherited non-syndromic sensorineural hearing loss (NSSHL). GJB2 mutations were found in 31.7% of the families, and the GJB2-35delG mutation accounted for 73.6% of all GJB2 mutations. The carrier frequency of GJB2-35delG in the normal Turkish population was found to be 1.17% (five in 429). In addition to the described W24X, 233delC, 120delE and R127H mutations, we also identified a novel mutation, Q80R, in the GJB2 gene. Interestingly, the Q80R allele was inherited on the same haplotype as V27I and E114G polymorphisms. As little is known about the mutation frequencies of most other recently identified gap- and tight-junction genes as a cause for hearing loss, we further screened our patients for mutations in GJB3 (Cx31), GJA1 (Cx43), DeltaGJB6-D13S1830 (Cx30) and the gene encoding the tight-junction protein, claudin 14 (CLDN14). Several novel polymorphisms, but no disease-associated mutations, were identified in the CLND14 and GJA1 genes, and we were unable to detect the DeltaGJB6-D13S1830 deletion. A novel putative mutation, P223T, was found in the GJB3 gene in heterozygous form in a family with two affected children. Our data shows that the frequency of GJB2 mutations in Turkish patients with autosomal-recessive NSSHL and the carrier rate of the GJB2-35delG mutation in the Turkish population, is much lower than described for other Mediterranean countries. Furthermore, mutations in other gap- and tight-junction proteins are not a frequent cause of hearing loss in Turkey.
authors.affiliation: Division of Medical Genetics, Child Health Institute, Istanbul University, Istanbul, Turkey. wollnik@superonline.com
authors.forename: O
authors.initials: O
authors.lastname: Uyguner
authors.forename: M
authors.initials: M
authors.lastname: Emiroglu
authors.forename: A
authors.initials: A
authors.lastname: Uzumcu
authors.forename: G
authors.initials: G
authors.lastname: Hafiz
authors.forename: A
authors.initials: A
authors.lastname: Ghanbari
authors.forename: N
authors.initials: N
authors.lastname: Baserer
authors.forename: M
authors.initials: M
authors.lastname: Yuksel-Apak
authors.forename: B
authors.initials: B
authors.lastname: Wollnik
mesh_terms: D019943:Amino Acid Substitution; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D017629:Gap Junctions / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D034381:Hearing Loss / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D019108:Tight Junctions / Q000235:genetics* / Q000378:metabolism; D014421:Turkey
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26