Abstract
The c.-23+1G>A splice site mutation is one of the most frequent mutations of gene GJB2 (Cx26, 13q11-q12) associated with congenital non-syndromic autosomal recessive deafness. This mutation is characterized by a wide spread from Eastern Siberia and Central Asia to Eastern Europe, the Middle East, and South Asia. It is currently unknown whether this mutation spread over such a vast territory as a result of the founder effect or there were several local centers of origin of this mutation. For the first time, on the basis of the analysis of variability of nine SNP markers, five different haplotypes in deaf patients homozygous for mutation c.-23+1G>A from six Eurasian populations were reconstructed. The structure of the haplotypes revealed in Yakuts, Russians, Evenks, Tuvinians, Mongols, and Turks makes it possible to assume that mutation c.-23+1G>A (GJB2) could have spread across Eurasia as a result of the founder effect. The greatest diversity of haplotypes with c.-23+1G>A was found in patients from Mongolia, which probably refers to the earlier period of expansion of haplotypes carrying this mutation on the territory of Central Asia.
References
Stenson, P.D., Mort, M., Ball, E.V., et al., The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine, Hum. Genet., 2014, vol. 133, no. 1, pp. 1–9. doi 10.1007/s00439-013-1358-4
Morell, R.J., Kim, H.J., Hood, L.J., et al., Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with non-syndromic recessive deafness, Nat. Engl. J. Med., 1998, vol. 339, pp. 1500–1505. doi 10.1056/nejm199811193392103
Van Laer, L., Coucke, P., Mueller, R.F., et al., A common founder for the 35delG GJB2 gene mutation in connexin 26 hearing impairment, J. Med. Genet., 2001, vol. 38, pp. 515–518. doi 10.1136/jmg.38.8.515
Yan, D., Park, H.-J., Ouyang, X.M., et al., Evidence of founder effect of the 235delC mutation of the GJB2 (connexin 26) in East Asians, Hum. Genet., 2003, vol. 114, pp. 44–50. doi 10.1007/s00439-003-1018-1
RamShankar, M., Girirajan, S. Dagan, O., et al., Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India, J. Med. Genet., 2003, vol. 40, no. 5. e68. doi 10.1136/jmg.40.5.e68
Gallant, E., Francey, L., Tsai, E.A., et al., Homozygosity for the V37I GJB2 mutation in fifteen probands with mild to moderate sensorineural hearing impairment: further confirmation of pathogenicity and haplotype analysis in Asian populations, Am. J. Med. Genet., Part A, 2013, vol. 161, no. 9, pp. 2148–2157. doi 10.1002/ajmg.a.36042
Barashkov, N.A., Dzhemileva, L.U., Fedorova, S.A., et al., 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, vol. 56, no. 8, pp. 631–639. doi 10.1038/jhg.2011.72
Tekin, M., Xia, X.-J., Erdenetungalag, R., et al., GJB2 mutations in Mongolia: complex alleles, low frequency, and reduced fitness of the deaf, Ann. Hum. Genet., 2010, vol. 74, no. 2, pp. 155–164. doi 10.1111/j.1469-1809.2010.00564.x
Seeman, P. and Sakmaryová, I., High prevalence of IVS1+1 to G>A/GJB2 mutation among Czech hearing impaired patients with monoallelic mutation in the coding region of GJB2, Clin. Genet., 2006, vol. 69, pp. 410–413. doi 10.1111/j.1399-0004.2006.00602.x
Pollak, A., Skórka, A., Mueller-Malesinska, M., et al., M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance, Am. J. Med. Genet., Part A, 2007, vol. 143A, pp. 2534–2543. doi 10.1002/ajmg.a.31982
Tóth, T., Kupka, S., Haack, B., et al., Coincidence of mutations in different connexin genes in Hungarian patients, Int. J. Mol. Med., 2007, vol. 20, pp. 315–321. doi 10.3892/ijmm.20.3.315
Sansovic, I., Knezevic, J., Musani, V., et al., GJB2 mutations in patients with nonsyndromic hearing loss from Croatia, Genet. Test. Mol. Biomarkers, 2009, vol. 13, no. 5, pp. 693–699. doi 10.1089/gtmb.2009.0073
Bliznets, E.A., Galkina, V.A., Matyushchenko, G.N., et al., Changes in the connexin 26 gene (GJB2) in Russian patients with hearing loss: results of long-term molecular diagnostics of hereditary nonsyndromic hearing loss, Russ. J. Genet., 2012, vol. 48, no. 1, pp. 101–112. doi 10.1134/S1022795412010036
Minárik, G., Tretinárová, D., Szemes, T., and Kádasi, L., Prevalence of DFNB1 mutations in Slovak patients with non-syndromic hearing loss, Int. J. Pediatr. Otorhinolaryngol., 2012, vol. 76, no. 3, pp. 400–403. doi 10.1016/j.ijporl.2011.12.020
Shubina-Oleinik, O., Siniauskaya, M., Merkulava, E., et al. When should one look for IVS1+1G>A splice mutation in patients with nonsyndromic sensorineural hearing loss?, JHS, 2014, vol. 4, no. 2, pp. 24–29. doi 10.17430/891018
Bozhkova, V.P., Khashaev, Z.Kh., and Magomedov, Sh.M., Study of hereditary hearing loss among children of the North Caucasus, Fundam. Issled., 2011, no. 5, pp. 23–27.
Sirmaci, A., Akcayoz-duman, D., and Tekin, M., The c. IVS1+1G>A mutation in the GJB2 gene is prevalent and large deletions involving the GJB6 gene are not present in the Turkish population, J. Genet., 2006, vol. 85, no. 3, pp. 213–216.
Bonyadi, M., Fotouhi, N., and Esmaeili, M., Prevalence of IVS1+1G>A mutation among Iranian Azeri Turkish patients with autosomal recessive non-syndromic hearing loss (ARNSHL), Int. J. Pediatr. Otorhinolaryngol., 2011, vol. 75, no. 12, pp. 1612–1615. doi 10.1016/j.ijporl.2011.09.024
Khalifa Alkowari, M., Girotto, G., Abdulhadi, K., et al., GJB2 and GJB6 genes and the A1555G mitochondrial mutation are only minor causes of nonsyndromic hearing loss in the Qatari population, Int. J. Audiol., 2012, vol. 51, pp. 181–185. doi 10.3109/14992027.2011.625983
Zeinali, S., Davoudi-Dehaghani, E., Azadmehr, S., et al., GJB2 c.-23+1G>A mutation is second most common mutation among Iranian individuals with autosomal recessive hearing loss, Eur. Arch. Otorhinolaryngol., 2015, vol. 272, no. 9, pp. 2255–2259. doi 10.1007/s00405-014-3171-7
Bajaj, Y., Sirimanna, T., Albert, D.M., et al., Spectrum of GJB2 mutations causing deafness in the British Bangladeshi population, Clin. Otolaryngol., 2008, vol. 33, pp. 313–318. doi 10.1111/j.1749-4486.2008.01754.x
Bady-Khoo, M.S., Bondar’, A.A., Morozov, I.V., et al., The study of inherited forms of hearing loss/deafness in the Republic of Tyva: 2. Assessment of the spectrum of GJB2 (Cx26) gene mutations and their contribution to the etiology of hearing loss, Med. Genet., 2014, vol. 13, no. 11, pp. 30–40.
1000 Genomes Project, The International Genome Sample Resource. http://www.1000genomes.org.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © A.V. Solovyev, N.A. Barashkov, M.S. Bady-Khoo, M.V. Zytsar, O.L. Posukh, G.P. Romanov, A.M. Rafailov, N.N. Sazonov, A.N. Alexeev, L.U. Dzhemileva, E.K. Khusnutdinova, S.A. Fedorova, 2017, published in Genetika, 2017, Vol. 53, No. 8, pp. 988–994.
Rights and permissions
About this article
Cite this article
Solovyev, A.V., Barashkov, N.A., Bady-Khoo, M.S. et al. Reconstruction of SNP haplotypes with mutation c.-23+1G>A in human gene GJB2 (Chromosome 13) in some populations of Eurasia. Russ J Genet 53, 936–941 (2017). https://doi.org/10.1134/S1022795417080099
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1022795417080099