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PLoS One. 2016 May 25;11(5):e0156300. doi: 10.1371/journal.pone.0156300. eCollection 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).

Author information

1
Department of Molecular Genetics, Federal State Budgetary Scientific Institution "Yakut Science Centre of Complex Medical Problems," Yakutsk, Russian Federation.
2
Laboratory of Molecular Biology, Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
3
Laboratory of Human Molecular Genetics, Federal Research Center, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
4
Novosibirsk State University, Novosibirsk, Russian Federation.
5
Department of Radiology, Republican Hospital # 2 -Center of Emergency Medicine, Ministry of Public Health of the Sakha Republic, Yakutsk, Russian Federation.
6
Republican Centre of Professional Pathology, Republican Hospital # 2 -Center of Emergency Medicine, Ministry of Public Health of the Sakha Republic, Yakutsk, Russian Federation.
7
Institute of Foreign Philology and Regional Studies, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
8
Audiology-Logopaedic Centre, Republican Hospital #1- National Medical Centre, Ministry of Public Health of the Sakha Republic, Yakutsk, Russian Federation.
9
SB RAS Genomics Core Facility, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
10
Department of Biochemistry and Biotechnology, Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
11
Institute of Humanitarian Research and Indigenous Peoples of the North, Siberian Branch of the Russian Academy of Sciences, Yakutsk, Russian Federation.
12
Laboratory of Human Molecular Genetics, Institute of Biochemistry and Genetics, Ufa Scientific Centre, Russian Academy of Sciences, Ufa, Russian Federation.
13
Department of Immunology and Human Reproductive Health, Bashkir State Medical University, Ufa, Russian Federation.
14
Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russian Federation.

Abstract

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.

PMID:
27224056
PMCID:
PMC4880331
DOI:
10.1371/journal.pone.0156300
[Indexed for MEDLINE]
Free PMC Article

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