The c.-259C>T mutation, previously described as -3438C>T, is not a common cause of non-syndromic hearing impairment alone or together with heterozygous pathogenic GJB2 mutations that are statistically overrepresented in non-syndromic hearing impaired patient groups.
We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI.
Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of non-syndromic recessive hearing impairment in many countries and are largely dependent on ethnic groups.
Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID) syndrome.
In contrast to the volume of information regarding the involvement of GJB2 mutations in hearing impairment in populations of European ancestry, less is known regarding other ethnic groups.
Because of its high frequency, DFNB1hearing impairment has received continued attention from researchers along the years, resulting in a wealth of data that is unparalleled among these disorders.
Verified GJB2-negative samples were subsequently subjected to whole exome sequencing (WES) to identify the underlying causes of hearing impairment, and the variants identified in each family were further confirmed by Sanger sequencing.
One mutation in GJB2, 35delG, accounts for a large percentage of GJB2hearing impairment in Southern Europe whereas a considerably lower frequency has been reported from Northern European populations.
Mutations in the GJB2 gene, which encodes the gap junction protein connexin 26 (Cx26), are the primary cause of hereditary prelingual hearing impairment.
Persons diagnosed with DFNB1 segregating two truncating/nonsense mutations had a more severe phenotype than persons carrying two missense mutations, with mean hearing impairments being 88 and 37%, respectively (P < 0.05).
We report here a non consanguineous assortatively mating hearing impaired family with one of the hearing impaired partners, their hearing impaired sibling and hearing impaired offspring showing compound heterozygosity in the GJB2 gene, involving a dominant mutation p.R184Q and two recessive mutations p.Q124X and c.IVS 1+1G>A in a unique triallelic combination.
Analyses of gap junction protein beta-2 and -6 genes revealed that similar pathological genotypes, occurring with similar frequencies, were responsible for progressive hearing loss, compared with reported genotypes for non-progressive hearing loss patients.