Prevalence of the IVS1(+1)G→A and 35delG mutations in the GJB2 gene of Turkish patients with nonsyndromic hearing loss

摘要

GJB2 encodes connexin 26, a gap junction protein that is assumed to be a component of the potassium recycling pathway in the inner ear. Loss or malfunction of these gap junctions, as might be refl ected by mutations in GJB2, may disrupt potassium movement from the hair cells through the supporting cell network to the endolymph, leading to hearing impairment. One mutation, the deletion of 1 guanosine residue from a stretch of 6 between nucleotide positions 30 and 35 (35delG) at codon 10, is the most common deafness-causing allelic variant of GJB2 in sporadic patients and autosomal recessive families. Mutations in the GJB2 gene represent the most common cause of autosomal recessive, sensorineural hearing loss. The 35delG mutation accounts for more than two-thirds of identified mutations. In this study, mutations, especially in the connexin 26 (GJB2), connexin 30 (GJB6), and 12srRNA genes, among 173 unrelated patients with prelingual nonsyndromic autosomal recessive deafness were screened and investigated by using the polymerase chain reactionbased restriction fragment length polymorphism (PCR-based RFLP), single-strand conformation polymorphism (SSCP), and sequence analysis methods. In patients with severe to profound hearing loss, 2 diff erent mutations and 1 polymorphism (35delG and IVS1(+1)G→A mutations and V153I polymorphism) were found. The 35delG mutation was detected as the most common pathogenic allele among the Turkish patients and accounted for 50% of all mutant GJB2 alleles. The 35delG and IVS1+1G→A mutations in the Cx26 gene were detected with total allele frequencies of 16.47% and 4.33%, respectively, and the V153 polymorphism was found in a heterozygous state at an allele frequency of 3.47%. However, the 342-kb deletion in the Cx30 gene and mitochondrial (mt)1555A→G in the 12srRNA gene mutations could not be detected among the studied patients.