7 research outputs found
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 region in 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
Prevalence of congenital HI caused by biallelic <i>GJB2</i> pathogenic variants in the Sakha Republic.
<p>Note: The territory of the Sakha Republic is shown in blue (bottom map). HI rates were calculated per 10,000 people, and appropriate data are presented only for the districts and cities of the Sakha Republic with population more than 10,000. Detailed data are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156300#pone.0156300.s001" target="_blank">S1 Table</a>.</p
Spectrum and Frequency of the <i>GJB2</i> Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic) - Fig 1
<p>Detected pathogenic and benign variants in the <i>GJB2</i> gene in patients (A) and control groups (B). Note: Pathogenic variants are shown in red, benign variants are shown in blue; *—unclassified variant, b.p.—base pair.</p
<i>GJB2</i> genotypes in patients with HI.
<p><i>GJB2</i> genotypes in patients with HI.</p
Carrier frequency of the major pathogenic variants of the <i>GJB2</i> gene in the Yakut and Russian control samples.
<p>Carrier frequency of the major pathogenic variants of the <i>GJB2</i> gene in the Yakut and Russian control samples.</p
Characteristics of the patients and control groups.
<p>Characteristics of the patients and control groups.</p