Identification of 605ins46, a novel GJB2 mutation in a Japanese family

GJB2 gene mutations in newborns with non-syndromic hearing impairment in Northern China

“…One patient had the compound heterozygous mutation of 605ins46 and 235delC. To date, the 605ins46 mutation was only detected in one Japanese family with hearing loss and was believed as pathological mutation (Yuge et al, 2002). The current report is the second of GJB2 insertion mutation with a long nucleotide sequence.…”

Carrier frequency of GJB2 (connexin-26) mutations causing inherited deafness in the Korean population

“…In this study, we evaluated the prevalence of GJB2 mutations causing inherited deafness in the Korean population, and eight different variants associated with inherited deafness were identified. The carrier frequency of GJB2 pathogenic mutations was 3% in 2,072 unrelated newborns with IC intracellular, TM transmembrane, EC extracellular a Novel sequence variant b The c.176_191del16 mutation was previously identified in Korean and Japanese individuals with nonsyndromic hearing loss (Park et al 2000;Abe et al 2000;Ohtsuka et al 2003) c The c.299-300delAT mutation has been reported, mainly Asians (Abe et al 2000;Park et al 2000) d One insertion mutation, c.605ins46, was previously found in a Japanese family with hearing loss (Yuge et al 2002) and in a newborn with hearing loss in Northern China (Shi et al 2004) e Classified in terms of their pathogenicity based on the PolyPhen and SNPs3D prediction softwares f The p.W3T was described as novel variant in the text and not counted for the carrier frequency of GJB2 pathogenic mutations normal hearing, which is similar to that found in the Caucasian population (2-3%) (Kelley et al 1998;Green et al 1999;Tang et al 2006). Taking into account this carrier frequency, 1 in every 4,468 subjects of the Korean general population would be homozygous or compound heterozygous for GJB2 mutations that cause inherited deafness.…”

A novel compound heterozygous mutation in the GJB2 gene causing non-syndromic hearing loss in a family

“…c.257C>G and c.605ins46 are rare GJB2 mutations that have previously been reported to segregate with hearing loss exclusively in East Asian populations, either homozygously (8,14–16) or as part of compound heterozygous mutations with other more prevalent mutations such as c.235delC and c.299delAT (8). It is theoretically a very improbable event for these two rare mutations to occur in one patient.…”

“…The c.257C>G mutation, which is located in the second transmembrane domain of Cx26, converts an uncharged amino acid (threonine) at codon 86 to a positively charged amino acid (arginine) and produces a functionally null protein (14). It is believed that the hearing loss caused by this mutation stems from its inability to localize to the cell membrane (16). c.605ins46, a frame-shift mutation, is sited in the fourth transmembrane domain of Cx26 and has a tandem repeat of 46 nucleotides at position 605.…”