The high frequency of GJB2 gene mutation c.313_326del14 suggests its possible origin in ancestors of Lithuanian population. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Mikstiene, Violeta; Jakaitiene, Audrone; Byckova, Jekaterina; Gradauskiene, Egle; Preiksaitiene, Egle; Burnyte, Birute; Tumiene, Birute; Matuleviciene, Ausra; Ambrozaityte, Laima; Uktveryte, Ingrida; Domarkiene, Ingrida; Rancelis, Tautvydas; Cimbalistiene, Loreta; Lesinskas, Eugenijus; Kucinskas, Vaidutis; Utkus, Algirdas
• Is Part Of: BMC genetics. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: Non-syndromic sensorineural hearing loss -- GJB2 and GJB6 genes -- c.313_326del14 mutation -- p.(Lys105Glyfs*5) -- Frequency of carriers of GJB2 gene mutation in the Lithuanian population; Genetics -- Periodicals; 576.505
• DOI: 10.1186/s12863-016-0354-9
• Languages: English
• ISSNs: 1471-2156

Abstract

Abstract Background Congenital hearing loss (CHL) is diagnosed in 1 – 2 newborns in 1000, genetic factors contribute to two thirds of CHL cases in industrialised countries. Mutations of theGJB2 gene located in theDFNB1 locus (13q11-12) are a major cause of CHL worldwide. The aim of this cross-sectional study was to assess the contribution of theDFNB1 locus containing theGJB2 andGJB6 genes in the development of early onset hearing loss in the affected group of participants, to determine the population-specific mutational profile andDFNB1 -related HL burden in Lithuanian population. Methods Clinical data were obtained from a collection of 158 affected participants (146 unrelated probands) with early onset non-syndromic HL.GJB2 andGJB6 gene sequencing andGJB6 gene deletion testing were performed. The data ofGJB2 andGJB6 gene sequencing in 98 participants in group of self-reported healthy Lithuanian inhabitants were analysed. Statistic summary, homogeneity tests, and logistic regression analysis were used for the assessment of genotype-phenotype correlation. Results Our findings show 57.5 % of affected participants with two pathogenicGJB2 gene mutations identified. The most prevalentGJB2 mutations were c.35delG, p. (Gly12Valfs*2) (rs80338939) and c.313_326del14, p. (Lys105Glyfs*5) (rs111033253) with allele frequencies 64.7 % and 28.3 % respectively.GJB6 gene mutations were not identified in the affected group of participants. The statistical analysis revealed significant differences betweenGJB2 (−) andGJB2 (+) groups in disease severity (p = 0.001), and family history (p = 0.01). The probability of identification ofGJB2 mutations in patients with various HL characteristics was estimated. The carrier rate ofGJB2 gene mutations – 7.1 % (~1 in 14) was identified in the group of healthy participants and a high frequency ofGJB2 -related hearing loss was estimated in our population. Discussion The results show a very high proportion of GJB2-positive individuals in the research group affected with sensorineural HL. The allele frequency of c.35delG mutation (64.7 %) is consistent with many previously published studies in groups of affected individuals of Caucasian populations. The high frequency of the c.313_326del14 (28.3 % of pathogenic alleles) mutation in affected group of participants was an unexpected finding in our study suggesting not only a high frequency of carriers of this mutation in our population but also its possible origin in Lithuanian ancestors. The high frequency of carriers of the c.313_326del14 mutation in the entire Lithuanian population is supported by it being identified twice in the ethnic Lithuanian group of healthy participants (a frequency 2.0 % of carriers in the study group). Conclusion Analysis of the allele frequency ofGJB2 gene mutations revealed a high proportion of c. 313_326del14 (rs111033253) mutations in theGJB2 -positive group suggesting its possible origin in Lithuanian forebears. The high frequency of carriers ofGJB2 gene mutations in the group of healthy participants corresponds to the substantial frequency ofGJB2 -associated HL in Lithuania. The observations of the study indicate the significant contribution ofGJB2 gene mutations to the pathogenesis of the disorder in the Lithuanian population and will contribute to introducing principles to predict the characteristics of the disease in patients.