The audiological analysis in the patients homozygous for the c.-23+1G>A mutation in the GJB2 gene presenting with the loss of hearing in Yakutiya

Abstract

In the course of previous investigations carried out in the Republic of Sakha (Yakutiya), we have identified the main molecular-genetic factor responsible for the hereditary impairment of hearing among the indigenous population (mostly the Yakuts).The disease was shown to be attributable to the c.-23+1G>A mutation localized in the splice donor site (exon 1) of the GJB2 (Cx26) gene. The present study involved the comprehensive audiological analysis of the patients homozygous for the c.-23+1G>A mutation in the GJB2 gene based on the results of the study of a large sample of the patients residing in Yakutiya. All individuals with the GJB2 genotype c.-23+1G>A/c.-23-1G>A (n=108) at the mean age of 14.32±4.7 years (all ethnic Yakuts)were examined with the use oftonal threshold audiometry for air conduction testing at the frequencies of 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and bone conduction testing at the frequencies of 0.25, 0.5, 1.0, and 4.0 with a step of 5.0 dB.The results of the ASSR test were used whenever tonal threshold audiometry proved impracticable The data obtained in the study characterize the allelic form of the disease associated with the GJB2 genotype c.-23+1G>A/c.-23-1G>A as the congenital bilateral symmetric (90.1%), sensorineural (90.1%) form of hearing impairment of variable severity (from grade 1 to complete deafness) with the «flat» audiological profile (median slope not more than 5.0 dB in the extended frequency range (EFR) of 0.5, 1.0, 2.0, and 4.0, kHz). It is concluded that the results of the audiological analysis performed in the present study give evidence of relatively homogeneous but variable in terms of severity impairment of hearing in the patients homozygous for the c.-23+1G>A mutation in the GJB2 (Cx26) gene. It may serve as a positive prognostic sign to be used in the development and prescription of hearing aids.

Update of spectrum c.35delG and c.‐23+1G>A mutations on the GJB2 gene in individuals with autosomal recessive nonsyndromic hearing loss

“…This mutation has been reported at different frequencies among different populations and is especially frequent in the Mongolian, Yakut, Czech, Hungarian, and Turkish HL populations (Barashkov et al., ; Teryutin, Barashkov, Kunel'skaya, Pshennikova, and Solov'ev, ; Yuan et al., ). It appears that the mutation in East Asia and North and South America is not abundant and has the highest frequency in South Asia and parts of the Middle East.…”

“…The c.−23+1G>A mutation is a pathogenic mutation caused HL autosomal recessive that is located in the noncoding exon 1 region (https://deafnessvariationdatabase.org/letter/g), which affects splicing of the GJB2 transcript (Angeli, 2008). This mutation has been reported at different frequencies among different populations and is especially frequent in the Mongolian, Yakut, Czech, Hungarian, and Turkish HL populations (Barashkov et al, 2016;Teryutin, Barashkov, Kunel'skaya, Pshennikova, and Solov'ev, 2016;Yuan et al, 2010). It appears that the mutation in East Asia and North and South America is not abundant and has the highest frequency in South Asia and parts of the Middle East.…”