Genotypes and phenotypes of a family with a deaf child carrying combined heterozygous mutations in SLC26A4 and GJB3 genes

Li,Yunlong; Zhu,Baosheng

doi:10.3892/mmr.2016.5280

Genotypes and phenotypes of a family with a deaf child carrying combined heterozygous mutations in SLC26A4 and GJB3 genes

Authors:
- Yunlong Li
- Baosheng Zhu
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Affiliations: Medical Faculty, Affiliated Hospital of Kunming University of Science and Technology (The First People's Hospital of Yunnan Province), Kunming University of Science and Technology, Kunming, Yunan 650500, P.R. China
Published online on: May 13, 2016 https://doi.org/10.3892/mmr.2016.5280
Pages: 319-324

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Abstract

Mutations in the SLC26A4 gene have been shown to cause a type of deafness referred to as large vestibular aqueduct syndrome (LVAS), whereas mutations in the GJB3 gene have been associated with nonsyndromic deafness. However, the clinical phenotypes of these mutations vary and remain to be fully elucidated. The present study performed genetic analysis of a Chinese family, in which the child was deaf and the parents were healthy. Sanger sequencing demonstrated that the affected individual harbored three heterogeneous mutations in the SLC26A4 and GJB3 genes, as follows: SLC26A4 IVS-2 A>G, SLC26A4 c.2168 A>G and GJB3 c.538 C>T. The affected individual exhibited hearing loss and was diagnosed with LVAS by computed tomography scan. The mother and father of the affected individual harbored the heterogeneous mutations of SLC26A4 IVS-2 A>G and GJB3 c.538 C>T, and the heterozygous mutation of SLC26A4 c.2168 A>G, respectively. Neither parents exhibited any hearing loss. The results obtained from the deaf patient provided genetic and clinical evidence that carrying combined heterogeneous mutations in the GJB3 and SLC26A4 genes may be involved in the etiology of severe hearing loss, of which the mechanism requires further examination.

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1	Lasak JM, Allen P, McVay T and Lewis D: Hearing loss: Diagnosis and management. Prim Care. 41:19–31. 2014. View Article : Google Scholar : PubMed/NCBI
2	Oishi N and Schacht J: Emerging treatments for noise-induced hearing loss. Expert Opin Emerg Drugs. 16:235–245. 2011. View Article : Google Scholar : PubMed/NCBI
3	Roizen NJ: Nongenetic causes of hearing loss. Ment Retard Dev Disabil Res Rev. 9:120–127. 2003. View Article : Google Scholar : PubMed/NCBI
4	Willems PJ: Genetic causes of hearing loss. N Engl J Med. 342:1101–1109. 2000. View Article : Google Scholar : PubMed/NCBI
5	Levenson D: New testing guidelines for hearing loss support next-generation sequencing: Testing method may help determine genetic causes of hearing loss among patients whose phenotypes are not easily distinguished clinically. Am J Med Genet A. 164A:vii–viii. 2014.
6	Wei Q, Wang S, Yao J, Lu Y, Chen Z, Xing G and Cao X: Genetic mutations of GJB2 and mitochondrial 12S rRNA in nonsyndromic hearing loss in Jiangsu Province of China. J Transl Med. 11:1632013. View Article : Google Scholar : PubMed/NCBI
7	Bicego M, Beltramello M, Melchionda S, Carella M, Piazza V, Zelante L, Bukauskas FF, Arslan E, Cama E, Pantano S, et al: Pathogenetic role of the deafness-related M34T mutation of Cx26. Hum Mol Genet. 15:2569–2587. 2006. View Article : Google Scholar : PubMed/NCBI
8	Frei K, Ramsebner R, Hamader G, Lucas T, Schoefer C, Baumgartner WD, Wachtler FJ and Kirschhofer K: Lack of association between Connexin 31 (GJB3) alterations and sensorineural deafness in Austria. Hear Res. 194:81–86. 2004. View Article : Google Scholar : PubMed/NCBI
9	Kokotas H, Grigoriadou M, Korres GS, Ferekidou E, Giannoulia-Karantana A, Kandiloros D, Korres S and Petersen MB: Are GJB2 mutations an aggravating factor in the phenotypic expression of mitochondrial non-syndromic deafness? J Hum Genet. 55:265–269. 2010. View Article : Google Scholar : PubMed/NCBI
10	Smith RJ and Robin NH: Genetic testing for deafness-GJB2 and SLC26A4 as causes of deafness. J Commun Disord. 35:367–377. 2002. View Article : Google Scholar : PubMed/NCBI
11	Estivill X, Govea N, Barceló E, Badenas C, Romero E, Moral L, Scozzri R, D'Urbano L, Zeviani M and Torroni A: Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides. Am J Hum Genet. 62:27–35. 1998. View Article : Google Scholar : PubMed/NCBI
12	Azaiez H, Yang T, Prasad S, Sorensen JL, Nishimura CJ, Kimberling WJ and Smith RJ: Genotype-phenotype correlations for SLC26A4-related deafness. Hum Genet. 122:451–457. 2007. View Article : Google Scholar : PubMed/NCBI
13	Oh SK, Choi SY, Yu SH, Lee KY, Hong JH, Hur SW, Kim SJ, Jeon CJ and Kim UK: Evaluation of the pathogenicity of GJB3 and GJB6 variants associated with nonsyndromic hearing loss. Biochim Biophys Acta. 1832:285–291. 2013. View Article : Google Scholar
14	Liu XZ, Yuan Y, Yan D, Ding EH, Ouyang XM, Fei Y, Tang W, Yuan H, Chang Q, Du LL, et al: Digenic inheritance of non-syndromic deafness caused by mutations at the gap junction proteins Cx26 and Cx31. Hum Genet. 125:53–62. 2009. View Article : Google Scholar :
15	Wang HW, Jia X, Ji Y, Kong QP, Zhang Q, Yao YG and Zhang YP: Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A. Mutat Res. 643:48–53. 2008. View Article : Google Scholar : PubMed/NCBI
16	Huang S, Wang G, Jiang Y, Yuan Y, Han D, Song Y and Dai P: Phenotype and genotype of deaf patients with combined genomic and mitochondrial inheritance models. Mitochondrion. 13:791–794. 2013. View Article : Google Scholar : PubMed/NCBI
17	Sagong B, Baek JI, Oh SK, Na KJ, Bae JW, Choi SY, Jeong JY, Choi JY, Lee SH, Lee KY and Kim UK: A rapid method for simultaneous screening of multi-gene mutations associated with hearing loss in the Korean population. PLoS One. 8:e572372013. View Article : Google Scholar : PubMed/NCBI
18	Du W, Cheng J, Ding H, Jiang Z, Guo Y and Yuan H: A rapid method for simultaneous multi-gene mutation screening in children with nonsyndromic hearing loss. Genomics. 104:264–270. 2014. View Article : Google Scholar : PubMed/NCBI
19	Smith RJH, Shearer AE, Hildebrand MS and Van Camp G: Deafness and hereditary hearing loss overview. GeneReviews® (Internet). Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH and Stephens K: University of Washington; Seattle, WA: pp. 1993–2016. 1993
20	Bitner-Glindzicz M: Hereditary deafness and phenotyping in humans. Br Med Bull. 63:73–94. 2002. View Article : Google Scholar : PubMed/NCBI