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Open Access 01-12-2018 | Research article

Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia

Authors: Marina V. Zytsar, Nikolay A. Barashkov, Marita S. Bady-Khoo, Olga A. Shubina-Olejnik, Nina G. Danilenko, Alexander A. Bondar, Igor V. Morozov, Aisen V. Solovyev, Valeriia Yu. Danilchenko, Vladimir N. Maximov, Olga L. Posukh

Published in: BMC Medical Genetics | Issue 1/2018

Abstract

Background

Mutations 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.

Methods

The 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.

Results

We 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).

Conclusions

Distribution 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.

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Stenson PD, Mort M, Ball EV, Evans K, Hayden M, Heywood S, Hussain M, Phillips AD, Cooper DN. The human gene mutation database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum Genet. 2017;136:665–77.CrossRefPubMedPubMedCentral

Chan DK, Chang KW. GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype. Laryngoscope. 2014; https://doi.org/10.1002/lary.24332.

Liu XZ, Xia XJ, Ke XM, Ouyang XM, Du LL, Liu YH, Angeli S, Telischi FF, Nance WE, Balkany T, et al. The prevalence of connexin 26 (GJB2) mutations in the Chinese population. Hum Genet. 2002;111:394–7.CrossRefPubMed

Ohtsuka A, Yuge I, Kimura S, Namba A, Abe S, Van Laer L, Van Camp G, Usami S. GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation. Hum Genet. 2003;112(4):329–33.PubMed

Morell RJ, Kim HJ, Hood LJ, Goforth L, Friderici K, Fisher R, Van Camp G, Berlin CI, Oddoux C, Ostrer H, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. N Engl J Med. 1998;339:1500–5.CrossRefPubMed

Hamelmann C, Amedofu GK, Albrecht K, Muntau B, Gelhaus A, Brobby GW, Horstmann RD. Pattern of connexin 26 (GJB2) mutations causing sensorineural hearing impairment in Ghana. Hum Mutat. 2001;18:84–5.CrossRefPubMed

RamShankar M, Girirajan S, Dagan O, Ravi Shankar HM, Jalvi R, Rangasayee R, Avraham KB, Anand A. Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India. J Med Genet. 2003;40:e68.CrossRefPubMedPubMedCentral

Alvarez A, del Castillo I, Villamar M, Aguirre LA, González-Neira A, Lopez-Nevot A, Moreno-Pelayo MA, Moreno F. High prevalence of the W24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss. Am J Med Genet A. 2005;137A:255–8.CrossRefPubMed

Wattanasirichaigoon D, Limwongse C, Jariengprasert C, Yenchitsomanus PT, Tocharoenthanaphol C, Thongnoppakhun W, Thawil C, Charoenpipop D, Pho-iam T, Thongpradit S, et al. High prevalence of V37I genetic variant in the connexin-26 (GJB2) gene among non-syndromic hearing-impaired and control Thai individuals. Clin Genet. 2004;66:452–60.CrossRefPubMed

10.

Barashkov NA, Dzhemileva LU, Fedorova SA, Teryutin FM, Posukh OL, Fedotova EE, Lobov SL, Khusnutdinova EK. Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>a in GJB2 gene as a result of founder effect. J Hum Genet. 2011;56:631–9.CrossRefPubMed

11.

Carranza C, Menendez I, Herrera M, Castellanos P, Amado C, Maldonado F, Rosales L, Escobar N, Guerra M, Alvarez D, et al. A Mayan founder mutation is a common cause of deafness in Guatemala. Clin Genet. 2016;89:461–5.CrossRefPubMed

12.

Gasparini P, Rabionet R, Barbujani G, Melçhionda S, Petersen M, Brøndum-Nielsen K, Metspalu A, Oitmaa E, Pisano M, Fortina P, et al. High carrier frequency of the 35delG deafness mutation in European populations. Eur J Hum Genet. 2000;8:19–23.CrossRefPubMed

13.

Mahdieh N, Rabbani B. Statistical study of 35delG mutation of GJB2 gene: a meta-analysis of carrier frequency. Int J Audiol. 2009;48:363–70.CrossRefPubMed

14.

Lucotte G, Diéterlen F. The 35delG mutation in the connexin 26 gene (GJB2) associated with congenital deafness: European carrier frequencies and evidence for its origin in ancient Greece. Genet Test. 2005;9:20–5.CrossRefPubMed

15.

Carrasquillo MM, Zlotogora J, Barges S, Chakravarti A. Two different connexin 26 mutations in an inbred kindred segregating non-syndromic recessive deafness: implications for genetic studies in isolated populations. Hum Mol Genet. 1997;6:2163–72.CrossRefPubMed

16.

Denoyelle F, Weil D, Maw MA, Wilcox SA, Lench NJ, Allen-Powell DR, Osborn AH, Dahl HH, Middleton A, Houseman MJ, et al. Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene. Hum Mol Genet. 1997;6:2173–7.CrossRefPubMed

17.

Tekin M, Akar N, Cin S, Blanton SH, Xia XJ, Liu XZ, Nance WE, Pandya A. Connexin 26 (GJB2) mutations in the Turkish population: implications for the origin and high frequency of the 35delG mutation in Caucasians. Hum Genet. 2001;108:385–9.CrossRefPubMed

18.

Van Laer L, Coucke P, Mueller RF, Caethoven G, Flothmann K, Prasad SD, Chamberlin GP, Houseman M, Taylor GR, Van de Heyning CM, et al. A common founder for the 35delG GJB2 gene mutation in connexin 26 hearing impairment. J Med Genet. 2001;38:515–8.CrossRefPubMedPubMedCentral

19.

Shahin H, Walsh T, Sobe T, Lynch E, King MC, Avraham KB, Kanaan M. Genetics of congenital deafness in the Palestinian population: multiple connexin 26 alleles with shared origins in the Middle East. Hum Genet. 2002;110:284–9.CrossRefPubMed

20.

Rothrock CR, Murgia A, Sartorato EL, Leonardi E, Wei S, Lebeis SL, Yu LE, Elfenbein JL, Fisher RA, Friderici KH. Connexin 26 35delG does not represent a mutational hotspot. Hum Genet. 2003;113(1):18–23.PubMed

21.

Balci B, Gerçeker FO, Aksoy S, Sennaroğlu G, Kalay E, Sennaroğlu L, Dinçer P. Identification of an ancestral haplotype of the 35delG mutation in the GJB2 (connexin 26) gene responsible for autosomal recessive non-syndromic hearing loss in families from the eastern Black Sea region in Turkey. Turk J Pediatr. 2005;47(3):213–21.PubMed

22.

Belguith H, Hajji S, Salem N, Charfeddine I, Lahmar I, Amor MB, Ouldim K, Chouery E, Driss N, Drira M, et al. Analysis of GJB2 mutation: evidence for a Mediterranean ancestor for the 35delG mutation. Clin Genet. 2005;68:188–9.CrossRefPubMed

23.

Tekin M, Boğoclu G, Arican ST, Orman MN, Tastan H, Elsobky E, Elsayed S, Akar N. Evidence for single origins of 35delG and delE120 mutations in the GJB2 gene in Anatolia. Clin Genet. 2005;67:31–7.CrossRefPubMed

24.

Abidi O, Boulouiz R, Nahili H, Imken L, Rouba H, Chafik A, Barakat A. The analysis of three markers flanking GJB2 gene suggests a single origin of the most common 35delG mutation in the Moroccan population. Biochem Biophys Res Commun. 2008;377:971–4.CrossRefPubMed

25.

Kokotas H, Van Laer L, Grigoriadou M, Iliadou V, Economides J, Pomoni S, Pampanos A, Eleftheriades N, Ferekidou E, Korres S, et al. Strong linkage disequilibrium for the frequent GJB2 35delG mutation in the Greek population. Am J Med Genet A. 2008;146A:2879–84.CrossRefPubMed

26.

Kokotas H, Grigoriadou M, Villamar M, Giannoulia-Karantana A, del Castillo I, Petersen MB. Hypothesizing an ancient Greek origin of the GJB2 35delG mutation: can science meet history? Genet Test Mol Biomarkers. 2010;14:183–7.CrossRefPubMed

27.

Norouzi V, Azizi H, Fattahi Z, Esteghamat F, Bazazzadegan N, Nishimura C, Nikzat N, Jalalvand K, Kahrizi K, Smith RJ, et al. Did the GJB2 35delG mutation originate in Iran? Am J Med Genet A. 2011;155A:2453–8.CrossRefPubMed

28.

Dzhemileva LU, Posukh OL, Barashkov NA, Fedorova SA, Teryutin FM, Akhmetova VL, Khidiyatova IM, Khusainova RI, Lobov SL, Khusnutdinova EK. Haplotype diversity and reconstruction of ancestral haplotype associated with the c.35delG mutation in the GJB2 (Cx26) gene among the Volgo-Ural populations of Russia. Acta Nat. 2011;3(3):52–63.

29.

Shubina-Olejnik OA. Genetic nature of non-syndromic sensorineural hearing impairment in Belarus. Institute of Genetics and Cytology, National Academy of Sciences, Minsk, Belarus: Dissertation; 2015.

30.

Khidiiatova IM, Dzhemileva LU, Khabibulin RM, Khusnutdinova EK. Frequency of the 35delG mutation of the connexin 26 gene (GJB2) in patients with non-syndromic autosome-recessive deafness from Bashkortostan and in ethnic groups of the Volga-Ural region. Mol Biol (Mosk). 2002;36(3):438–41.

31.

Markova TG, Megrelishvilli SM, Zaĭtseva NG, Shagina IA, Poliakov AV. DNA diagnosis in congenital and early childhood hypoacusis and deafness. Vestn Otorinolaringol. 2002;6:12–5.

32.

Shokarev RA, Amelina SS, Kriventsova NV, Elchinova GI, Khlebnikova OV, Tverskaya SM, Bliznetz EA, Polyakov AV, Zinchenko RA. Genetic-epidemiological and molecular study of hereditary deafness in Rostov province. Medizinskaya genetika. 2005;4:556–65. Article in Russian

33.

Markova TG, Poliakova AV, Kunel'skaia NL. Clinical picture of hearing defects caused by Cx26 gene mutations. Vestn Otorinolaringol. 2008;2:4–9.

34.

Osetrova AA, YeI S, Rossinskaya TG, Galkina VA, Zinchenko RA. Investigation of genetic aspects of congenital and early childhood deafness in specialized schools for children with impaired hearing of Kirov region, Russia. Medizinskaya genetika. 2010;9:30–40. Article in Russian

35.

Bliznets EA, Galkina VA, Matiushchenko GN, Kisina AG, Markova TG, Poliakov AV. Changes in the connexin 26 (GJB2) gene in Russian patients with hearing disorders: results of long-term molecular diagnostics of hereditary nonsyndromic deafness. Genetika. 2012;48(1):112–24.PubMed

36.

Zinchenko RA, Osetrova AA, Sharonova EI. Hereditary deafness in Kirov oblast: estimation of the incidence rate and DNA diagnosis in children. Genetika. 2012;48(4):542–50.PubMed

37.

Lalaiants MR, Markova TG, Bakhshinian VV, Bliznets EA, Poliakov AV, Tavartikiladze GA. The audiological phenotype and the prevalence of GJB2-related sensorineural loss of hearing in the infants suffering acoustic disturbances. Vestn Otorinolaringol. 2014;2:37–43.

38.

Bliznetz EA, Lalayants MR, Markova TG, Balanovsky OP, Balanovska EV, Skhalyakho RA, Pocheshkhova EA, Nikitina NV, Voronin SV, Kudryashova EK, et al. Update of the GJB2/DFNB1 mutation spectrum in Russia: a founder Ingush mutation del(GJB2-D13S175) is the most frequent among other large deletions. J Hum Genet. 2017;62:789–95.CrossRefPubMedPubMedCentral

39.

Posukh O, Pallares-Ruiz N, Tadinova V, Osipova L, Claustres M, Roux AF. First molecular screening of deafness in the Altai Republic population. BMC Med Genet. 2005;6:12.CrossRefPubMedPubMedCentral

40.

Bady-Khoo MS, Bondar AA, Morozov IV, Zytsar MV, Mikhalskaya VYu, Skidanova OV, Barashkov NA, Mongush, RSh, Omzar OS, Tukar VM, et al. Study of hereditary forms of hearing loss in the Republic of Tyva. II. Evaluation of the mutational spectrum of the GJB2 (Cx26) gene and its contribution to the etiology of hearing loss Medizinskaya genetika. 2014;13:30–40. [Article in Russian].

41.

Barashkov NA, Pshennikova VG, Posukh OL, Teryutin FM, Solovyev AV, Klarov LA, Romanov GP, Gotovtsev NN, Kozhevnikov AA, Kirillina EV, et al. 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. 2016; https://doi.org/10.1371/journal.pone.0156300.

42.

Storm K, Willocx S, Flothmann K, Van Camp G. Determination of the carrier frequency of the common GJB2 (connexin-26) 35delG mutation in the Belgian population using an easy and reliable screening method. Hum Mutat. 1999;14:263–6.CrossRefPubMed

43.

Excoffier L, Lischer HE. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and windows. Mol Ecol Resour. 2010;10(3):564–7.CrossRefPubMed

44.

Bengtsson BO, Thomson G. Measuring the strength of associations between HLA antigens and diseases. Tissue Antigens. 1981;18:356–63.CrossRefPubMed

45.

Risch N, de Leon D, Ozelius L, Kramer P, Almasy L, Singer B, Fahn S, Breakefield X, Bressman S. Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population. Nat Genet. 1995;9:152–9.CrossRefPubMed

46.

Zhuravskiy SG, Ivanov SA, Taraskina AE, Grinchik OV, Kurus AA. Prevalence of GJB2 gene mutation 35delG among healthy population of Northwest Region of Russia. Meditsinskiy Akademicheskiy Zhurnal. 2009;9:41–5. Article in Russian

47.

Teek R, Kruustük K, Zordania R, Joost K, Reimand T, Möls T, Oitmaa E, Kahre T, Tõnisson N, Ounap K. Prevalence of c.35delG and p.M34T mutations in the GJB2 gene in Estonia. Int J Pediatr Otorhinolaryngol. 2010;74:1007–12.CrossRefPubMed

48.

Dzhemileva LU, Barashkov NA, Posukh OL, Khusainova RI, Akhmetova VL, Kutuev IA, Gilyazova IR, Tadinova VN, Fedorova SA, Khidiyatova IM, et al. Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia. J Hum Genet. 2010;55:749–54.CrossRefPubMed

49.

Bliznetz EA, Sarkisian TF, Manoukyan TÀ, Bakhshinyan VV, Polyakov AV. GJB2 caused hearing loss in Armenians. Medizinskaya genetika. 2012;5:23–8. Article in Russian

50.

Petrina NE, Bliznetz EA, Zinchenko RA, AKh.-M M, Petrova NA, Vasilyeva TA, Chudakova LV, Petrin AN, Polyakov AV, Ginter EK. The frequency of GJB2 gene mutations in patients with hereditary non-syndromic sensoneural hearing loss in eight populations of Karachay-Cherkess Republic. Medizinskaya genetika. 2017;16:19–25. Article in Russian

51.

Okladnikov AP, editor. Istoriya Sibiri s drevneishikh vremen do nashikh dnei [History of Siberia since ancient times to the present day]. Leningrad: Nauka; 1968. [in Russian]

52.

Lazaridis I, Patterson N, Mittnik A, Renaud G, Mallick S, Kirsanow K, Sudmant PH, Schraiber JG, Castellano S, Lipson M, et al. Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature. 2014;513:409–13.CrossRefPubMedPubMedCentral

53.

Ensemble genome browser. http://www.ensembl.org. Accessed Mar 2018.

54.

NCBI Probe Database. http://www.ncbi.nlm.nih.gov/probe. Accessed Mar 2018.

Title: Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia
Authors: Marina V. Zytsar
Nikolay A. Barashkov
Marita S. Bady-Khoo
Olga A. Shubina-Olejnik
Nina G. Danilenko
Alexander A. Bondar
Igor V. Morozov
Aisen V. Solovyev
Valeriia Yu. Danilchenko
Vladimir N. Maximov
Olga L. Posukh
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-018-0650-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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