SPECTRUM AND FREQUENCY OF THE GJB2 GENE PATHOGENIC VARIANTS IN A LARGE COHORT OF PATIENTS WITH HEARING IMPAIRMENT LIVING IN A SUBARCTIC REGION OF RUSSIA (THE SAKHA REPUBLIC)
Pathogenic variants in the GJB2 gene, encoding connexin 26, are known to be a major
cause of hearing impairment (HI). More than 300 allelic variants have been identified in the
GJB2 gene. Spectrum and allelic frequencies of the GJB2 gene vary significantly among different
ethnic groups worldwide. Until now, the spectrum and frequency of the pathogenic
variants in exon 1, exon 2 and the flanking intronic regions of the GJB2 gene have not been
described thoroughly in the Sakha Republic (Yakutia), which is located in a subarctic regionin Russia. The complete sequencing of the non-coding and coding regions of the GJB2
gene was performed in 393 patients with HI (Yakuts—296, Russians—51, mixed and other
ethnicities—46) and in 187 normal hearing individuals of Yakut (n = 107) and Russian (n =
80) populations. In the total sample (n = 580), we revealed 12 allelic variants of the GJB2
gene, 8 of which were recessive pathogenic variants. Ten genotypes with biallelic recessive
pathogenic variants in the GJB2 gene (in a homozygous or a compound heterozygous
state) were found in 192 out of 393 patients (48.85%). We found that the most frequent
GJB2 pathogenic variant in the Yakut patients was c.-23+1G>A (51.82%) and that the second
most frequent was c.109G>A (2.37%), followed by c.35delG (1.64%). Pathogenic variants
с.35delG (22.34%), c.-23+1G>A (5.31%), and c.313_326del14 (2.12%) were found to
be the most frequent among the Russian patients. The carrier frequencies of the c.-23
+1G>A and с.109G>A pathogenic variants in the Yakut control group were 10.20% and
2.80%, respectively. The carrier frequencies of с.35delG and c.101T>C were identical
(2.5%) in the Russian control group. We found that the contribution of the GJB2 gene pathogenic
variants in HI in the population of the Sakha Republic (48.85%) was the highest
among all of the previously studied regions of Asia. We suggest that extensive accumulation
of the c.-23+1G>A pathogenic variant in the indigenous Yakut population (92.20% of all
mutant chromosomes in patients) and an extremely high (10.20%) carrier frequency in the
control group may indicate a possible selective advantage for the c.-23+1G>A carriers living
in subarctic climate.
Библиографическое описание: : Barashkov NA, Pshennikova VG, Posukh OL, Teryutin FM, Solovyev AV, Klarov LA, et al. (2016) Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic). PLoS ONE 11(5): e0156300. doi:10.1371/journal.pone.0156300