Spectrum and frequency ofGJB2mutations in a cohort of 264 Portuguese nonsyndromic sensorineural hearing loss patients

Abstract

This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families.

Prevalence of 35delG and Met34Thr GJB2 variants in Portuguese samples

“…GJB2 encodes gap junction protein connexin 26 (Cx26), which has been implicated in the maintenance of K + homeostasis in the inner ear [4]. also the most common GJB2 mutation causing NSHL in Portugal, with a prevalence of 15.9% [6].…”

“…Another variation in the GJB2 gene that has been found with a high prevalence in studies in NSHL populations, including Portugal, c.101 T ! C (Met34Thr), a methionine-to-threonine substitution at amino acid 34 [2,6,10]. This variant was found at a lower frequency in NSHL patients, compared to the 35delG mutation [11].…”

SNPscan as a high-performance screening tool for mutation hotspots of hearing loss-associated genes

“…Eighteen additional variant alleles were detected by SNPscan. In terms of the positive rate comparison, although the pathogenicity of the variant c.109G N A in the GJB2 gene remains questionable, most recent studies suggest that this site change is a pathological mutation [16,17]. Hence, the positive rate of the SNPscan kit is 51.2%, which is higher than the 44.4% of the 15 loci SNaPshot analysis system.…”

“…About 28 kinds of variants were pathological mutations, which have been determined previously. The category of one nucleotide change was unknown (c.109G N A in the GJB2 gene), although most recent studies suggested that this site change is a pathological mutation [16,17]. The most prevalent mutation in these subjects was c.235delC in the GJB2 gene, and this mutation accounts for 40.0% (76/190) of all mutant alleles.…”

The controversial p.Met34Thr variant in GJB2 gene: Two siblings, one genotype, two phenotypes

“…Pollak et al (2007) [24] studied carriers of the p.Met34Thr/ c.35delG compound heterozygosity and also concluded that the p.Met34Thr variant presents a pathogenic role, with low penetrance and late onset and progressive HL. In our previous work (Matos et al, 2013) [25], we have observed the p.Met34Thr variant in 1,3% of the GJB2 alleles among 264 Portuguese nonsyndromic sensorineural HL patients. Two of these patients presented the p.Met34Thr/c.35delG and p.Met34Thr/p.Val95Met compound genotypes, respectively.…”