We concluded that p.Met34Thr and p.Val37Ile variants in GJB2 are pathogenic for autosomal recessive nonsyndromic hearing loss with variable expressivity and incomplete penetrance.
Mutations of the gap junction beta-2 protein (GJB2) gene located in the nonsyndromic hearing loss and deafness (DFNB1) locus (chromosome 13q11-12) are the main causes of autosomal recessive nonsyndromic hearing loss worldwide, but important differences exist between various populations.
Hence, recurrent monoallelic cases, who present the most common hereditary type of nonsyndromic hearing loss (i.e., DFNB1), carry only one identified pathogenic allele.
Cx26 mutation and expression abnormality are closely associated with inherited nonsyndromic deafness, but the association between Cx26 and prenatal hypoxia is less established.
Here we report three novel dominant GJB2 variants (p.Thr55Ala, p.Gln57_Pro58delinsHisSer, and p.Trp44Gly); two associated with syndromic sensorineural hearing loss and one with nonsyndromic hearing loss.
Aim of this study was to investigate the role of SLC26A4 coding mutations in a nonsyndromic hearing impairment (NSHI) patient group bearing heterozygous GJB235delG mutations.
We have previously shown that in vitro transduction with bovine adeno-associated viral (BAAV) vectors restores connexin expression and rescues gap junction coupling in cochlear organotypic cultures from connexin-deficient mice that are models DFNB1nonsyndromic hearing loss and deafness.
Although hundreds of genes have been reported to be associated with nonsyndromic hearing loss (NSHL), GJB2, GJB6, SLC26A4, and mitochondrial (mt) MT-RNR1 and MTTS are the major contributors.
However, GJB2 mutation is not associated with a significantly better prognosis when compared with those whose deafness results from either nonsyndromic hearing loss of unknown origin or other types of genetic mutations in the absence of other neurologic deficits.
Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss.
K<sup>+</sup>-recycling defect is a long-standing hypothesis for deafness mechanism of Connexin26 (Cx26, <i>GJB2</i>) mutations, which cause the most common hereditary deafness and are responsible for >50% of nonsyndromic hearing loss.
We aim to screen the mutations of 3 hearing loss (HL) genes (GJB2, SLC26A4, and 12S rRNA) in 71 cases with nonsyndromic hearing loss (NSHL) using microarray and SNPscan, and identify the roles of nonhotspot mutation of these genes in the screening of NSHL.
Although there are nearly 100 different causative genes identified for nonsyndromic hearing loss (NSHL), Sanger sequencing-based DNA diagnostics usually only analyses three, namely, GJB2, SLC26A4, and OTOF.
Findings suggest that genetic evaluation has a role as a complementary modality in HL evaluation for pediatric unilateral SNHL although it may not be necessary to analyze for various abnormalities other than connexin 26 when practising in a limited resources environment.
Pathogenic variants at the DFNB1 locus encompassing the GJB2 and GJB6 genes account for 50% of autosomal-recessive, congenital nonsyndromic hearing loss in the United States.