Dataset Information

Unique Mutational Spectrum of the GJB2 Gene and its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys).

ABSTRACT: Mutations in the GJB2 gene are the main cause for nonsyndromic autosomal recessive deafness 1A (DFNB1A) in many populations. GJB2 mutational spectrum and pathogenic contribution are widely varying in different populations. Significant efforts have been made worldwide to define DFNB1A molecular epidemiology, but this issue still remains open for some populations. The main aim of study is to estimate the DFNB1A prevalence and GJB2 mutational spectrum in Tuvinians-an indigenous population of the Tyva Republic (Southern Siberia, Russia). Sanger sequencing was applied to analysis of coding (exon 2) and non-coding regions of GJB2 in a cohort of Tuvinian patients with hearing impairments (n = 220) and ethnically matched controls (n = 157). Diagnosis of DFNB1A was established for 22.3% patients (28.8% of familial vs 18.6% of sporadic cases). Our results support that patients with monoallelic GJB2 mutations (8.2%) are coincidental carriers. Recessive mutations p.Trp172Cys, c.-23+1G>A, c.235delC, c.299_300delAT, p.Val37Ile and several benign variants were found in examined patients. A striking finding was a high prevalence of rare variant p.Trp172Cys (c.516G>C) in Tuvinians accounting for 62.9% of all mutant GJB2 alleles and a carrier frequency of 3.8% in controls. All obtained data provide important targeted information for genetic counseling of affected Tuvinian families and enrich current information on variability of GJB2 worldwide.

SUBMITTER: Posukh OL

PROVIDER: S-EPMC6627114 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Unique Mutational Spectrum of the GJB2 Gene and its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys).

Posukh Olga L OL Zytsar Marina V MV Bady-Khoo Marita S MS Danilchenko Valeria Yu VY Maslova Ekaterina A EA Barashkov Nikolay A NA Bondar Alexander A AA Morozov Igor V IV Maximov Vladimir N VN Voevoda Michael I MI

Genes 20190605 6

Mutations in the GJB2 gene are the main cause for nonsyndromic autosomal recessive deafness 1A (DFNB1A) in many populations. GJB2 mutational spectrum and pathogenic contribution are widely varying in different populations. Significant efforts have been made worldwide to define DFNB1A molecular epidemiology, but this issue still remains open for some populations. The main aim of study is to estimate the DFNB1A prevalence and GJB2 mutational spectrum in Tuvinians-an indigenous ...[more]

PMID: 31195736

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Project description:BackgroundThe paper presents the initiative on literature-based occurrence data mobilisation of fungi and fungi-related organisms (literature-based occurrences, Darwin Core MaterialCitation) to develop the Fungal literature-based occurrence database for the southern West Siberia (FuSWS). The initiative on mobilisation of literature-based occurrence data started in the northern part of West Siberia in 2016. The present project extends the initiative to the southern regions and includes ten administrative territories (Tyumen Region, Sverdlovsk Region, Chelyabinsk Region, Omsk Region, Kurgan Region, Tomsk Region, Novosibirsk Region, Kemerovo Region, Altai Territory and Republic of Altai). The area occupies the central to southern part of the West Siberian Plain and extends for about 1.5 K km from the west to the east from the eastern slopes of the Ural Mountains to Yenisey River and from north to south-about 1.3 K km. The total area equals about 1.4 million km2.The initiative is actively growing in spatial, collaboration and data accumulation terms. The working group of about 30 mycologists from eight organisations dedicated to the data mobilisation was created as part of the Siberian Mycological Society (informal organisation since 2019). They have compiled the almost complete bibliographic list of mycology-related papers for the southern West Siberia, including over 900 publications for the last two centuries (the earliest dated 1800). All literature sources were digitised and an online library was created to integrate bibliography metadata and digitised papers using Zotero bibliography manager. The analysis of published sources showed that about two-thirds of works contain occurrences of fungi for the scope of mobilisation.At the time of the paper submission, the database had been populated with a total of about 8 K records from 93 sources. The dataset is uploaded to GBIF, where it is available for online search of species occurrences and/or download. The project's page with the introduction, templates, bibliography list, video-presentations and written instructions is available (in Russian) at the web site of the Siberian Mycological Society. The initiative will be continued in the following years to extract the records from all published sources.New informationThe paper presents the first project with the aim of literature-based occurrence data mobilisation of fungi and fungi-related organisms in the southern West Siberia. The full bibliography and a digital library of all regional mycological publications created for the first time includes about 900 published works. By the time of paper submission, nearly 8 K occurrence records were extracted from about 90 literature sources and integrated into the FuSWS database published in GBIF.

Project description:BackgroundMutations in GJB2 gene are a major causes of deafness and their spectrum and prevalence are specific for various populations. The well-known mutation c.35delG is more frequent in populations of Caucasian origin. Data on the c.35delG prevalence in Russia are mainly restricted to the European part of this country. We aimed to estimate the carrier frequency of c.35delG in Western Siberia and thereby update current data on the c.35delG prevalence in Russia. According to a generally accepted hypothesis, c.35delG originated from a common ancestor in the Middle East or the Mediterranean ~ 10,000-14,000 years ago and spread throughout Europe with Neolithic migrations. To test the c.35delG common origin hypothesis, we have reconstructed haplotypes bearing c.35delG and evaluated the approximate age of c.35delG in Siberia.MethodsThe carrier frequency of c.35delG was estimated in 122 unrelated hearing individuals living in Western Siberia. For reconstruction of haplotypes bearing c.35delG, polymorphic D13S141, D13S175, D13S1853 flanking the GJB2 gene, and intragenic rs3751385 were genotyped in deaf patients homozygous for c.35delG (n = 24) and in unrelated healthy individuals negative for c.35delG (n = 67) living in Siberia.ResultsWe present updated carrier rates for c.35delG in Russia complemented by new data on c.35delG carrier frequency in Russians living in Western Siberia (4.1%). Two common D13S141-c.35delG-D13S175-D13S1853 haplotypes, 126-c.35delG-105-202 and 124-c.35delG-105-202, were reconstructed in the c.35delG homozygotes from Siberia. Moreover, identical allelic composition of the two most frequent c.35delG haplotypes restricted by D13S141 and D13S175 was established in geographically remote regions: Siberia and Volga-Ural region (Russia) and Belarus (Eastern Europe).ConclusionsDistribution of the c.35delG carrier frequency in Russia is characterized by pronounced ethno-geographic specificity with a downward trend from west to east. Comparative analysis of the c.35delG haplotypes supports a common origin of c.35delG in some regions of Russia (Volga-Ural region and Siberia) and in Eastern Europe (Belarus). A rough estimation of the c.35delG age in Siberia (about 4800 to 8100 years ago) probably reflects the early formation stages of the modern European population (including the European part of the contemporary territory of Russia) since the settlement of Siberia by Russians started only at the end of sixteenth century.

Dataset Information

Unique Mutational Spectrum of the GJB2 Gene and its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys).

Publications

Unique Mutational Spectrum of the <i>GJB2</i> Gene and its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys).

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