Genetic counseling for patients with nonsyndromic hearing impairment directed by gene analysis

Ma,Dingyuan; Zhang,Jingjing; Luo,Chunyu; Lin,Ying; Ji,Xiuqing; Hu,Ping; Xu,Zhengfeng

doi:10.3892/mmr.2016.4769

Genetic counseling for patients with nonsyndromic hearing impairment directed by gene analysis

Authors:
- Dingyuan Ma
- Jingjing Zhang
- Chunyu Luo
- Ying Lin
- Xiuqing Ji
- Ping Hu
- Zhengfeng Xu
View Affiliations

Affiliations: Department of Prenatal Diagnosis, State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: January 13, 2016 https://doi.org/10.3892/mmr.2016.4769
Pages: 1967-1974
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the genetic etiology of patients with nonsyndromic hearing impairment through gene analysis, and provide accurate genetic counseling and prenatal diagnosis for deaf patients and families with deaf children. Previous molecular etiological studies have demonstrated that the most common molecular changes in Chinese patients with nonsyndromic hearing loss (NSHL) involved gap junction protein β 2, solute carrier family 26, member 4 (SLC26A4), and mitochondrial DNA 12S rRNA. A total of 117 unrelated NSHL patients were included. Mutation screening was performed by Sanger sequencing in GJB2, 12S rRNA, and the hot‑spot regions of SLC26A4. In addition, patients with a single mutation of SLC26A4 in the hot‑spot regions underwent complete exon sequencing to identify a mutation in the other allele. A total of 36 of the 117 deaf patients were confirmed to have two pathogenic mutations, which included 4 deaf couples, husband or wife in 11 deaf couples and 17 deaf individuals. In addition, prenatal diagnoses was performed in 7 pregnant women at 18‑21 weeks gestation who had previously given birth to a deaf child, and the results showed that two fetal genotypes were the same as the proband's genotypes, four fetuses carried one pathogenic gene from their parents, and one fetus was identified to have no mutations. Taken together, the genetic testing of deaf patients can provide reasonable guidance to deaf patients and families with deaf children.

View Figures

View References

1	Shearer AE and Smith RJ: Genetics: Advances in genetic testing for deafness. Curr Opin Pediatr. 24:679–686. 2012. View Article : Google Scholar : PubMed/NCBI
2	Cryns K and Van Camp G: Deafness genes and their diagnostic applications. Audiol Neurootol. 9:2–22. 2004. View Article : Google Scholar
3	Hoefsloot LH, Feenstra I, Kunst HP and Kremer H: Genotype phenotype correlations for hearing impairment: Approaches to management. Clin Genet. 85:514–523. 2014. View Article : Google Scholar : PubMed/NCBI
4	Rabionet R, Gasparini P and Estivill X: Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins. Hum Mutat. 16:190–202. 2000. View Article : Google Scholar : PubMed/NCBI
5	Kenneson A, Van Naarden Braun K and Boyle C: GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: A HuGE review. Genet Med. 4:258–274. 2002. View Article : Google Scholar : PubMed/NCBI
6	Snoeckx RL, Huygen PL, Feldmann D, Marlin S, Denoyelle F, Waligora J, Mueller-Malesinska M, Pollak A, Ploski R, Murgia A, et al: GJB2 mutations and degree of hearing loss: A multicenter study. Am J Hum Genet. 77:945–957. 2005. View Article : Google Scholar : PubMed/NCBI
7	Ohtsuka A, Yuge I, Kimura S, Namba A, Abe S, Van Laer L, Van Camp G and Usami S: GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation. Hum Genet. 112:329–333. 2003.PubMed/NCBI
8	Hilgert N, Smith RJ and Van Camp G: Forty-six genes causing nonsyndromic hearing impairment: Which ones should be analyzed in DNA diagnostics? Mutat Res. 681:189–196. 2009. View Article : Google Scholar
9	Wang QJ, Zhao YL, Rao SQ, Guo YF, Yuan H, Zong L, Guan J, Xu BC, Wang DY, Han MK, et al: A distinct spectrum of SLC26A4 mutations in patients with enlarged vestibular aqueduct in China. Clin Genet. 72:245–254. 2007. View Article : Google Scholar : PubMed/NCBI
10	Du W, Guo Y, Wang C, Wang Y and Liu X: A systematic review and meta-analysis of common mutations of SLC26A4 gene in Asian populations. Int J Pediatr Otorhinolaryngol. 77:1670–1676. 2013. View Article : Google Scholar : PubMed/NCBI
11	Kokotas H, Petersen MB and Willems PJ: Mitochondrial deafness. Clin Genet. 71:379–391. 2007. View Article : Google Scholar : PubMed/NCBI
12	Yuan Y, You Y, Huang D, Cui J, Wang Y, Wang Q, Yu F, Kang D, Yuan H, Han D and Dai P: Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from typical areas in China. J Transl Med. 7:792009. View Article : Google Scholar : PubMed/NCBI
13	Dai P, Yu F, Han B, Liu X, Wang G, Li Q, Yuan Y, Liu X, Huang D, Kang D, et al: GJB2 mutation spectrum in 2,063 Chinese patients with nonsyndromic hearing impairment. J Transl Med. 7:262009. View Article : Google Scholar : PubMed/NCBI
14	Yuan Y, Guo W, Tang J, Zhang G, Wang G, Han M, Zhang X, Yang S, He DZ and Dai P: Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China. PLoS One. 7:e499842012. View Article : Google Scholar : PubMed/NCBI
15	Li Z, Li R, Chen J, Liao Z, Zhu Y, Qian Y, Xiong S, Heman-Ackah S, Wu J, Choo DI and Guan MX: Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. Hum Genet. 117:9–15. 2005. View Article : Google Scholar : PubMed/NCBI
16	Estivill X, Fortina P, Surrey S, Rabionet R, Melchionda S, D'Agruma L, Mansfield E, Rappaport E, Govea N, Milà M, et al: Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet. 351:394–398. 1998. View Article : Google Scholar : PubMed/NCBI
17	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. 339:1500–1505. 1998. View Article : Google Scholar : PubMed/NCBI
18	Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS, Cortopassi GA, Jaber L and Rotter JI: Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet. 4:289–294. 1993. View Article : Google Scholar : PubMed/NCBI
19	Zhao H, Li R, Wang Q, Yan Q, Deng JH, Han D, Bai Y, Young WY and Guan MX: Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family. Am J Hum Genet. 74:139–152. 2004. View Article : Google Scholar
20	Pryor SP, Madeo AC, Reynolds JC, Sarlis NJ, Arnos KS, Nance WE, Yang Y, Zalewski CK, Brewer CC, Butman JA and Griffith AJ: SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): Evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities. J Med Genet. 42:159–165. 2005. View Article : Google Scholar : PubMed/NCBI
21	Li Q, Zhu QW, Yuan YY, Huang SS, Han DY, Huang DL and Dai P: Identification of SLC26A4 c.919-2A>G compound heterozygosity in hearing-impaired patients to improve genetic counseling. J Transl Med. 10:2252012. View Article : Google Scholar :
22	Sun SC, Liu YX, Peng YS, Li HF and Xie CY: Analysis of GJB2 gene coding sequence in patients with nonsyndromic hearing loss. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 28:409–413. 2011.In Chinese. PubMed/NCBI
23	Dai P, Stewart AK, Chebib F, Hsu A, Rozenfeld J, Huang D, Kang D, Lip V, Fang H, Shao H, et al: Distinct and novel SLC26A4/Pendrin mutations in Chinese and U.S. patients with nonsyndromic hearing loss. Physiol Genomics. 38:281–290. 2009. View Article : Google Scholar : PubMed/NCBI
24	Chun JY, Shin SK, Min KT, Cho W, Kim J, Kim SO and Hong SP: Performance evaluation of the TheraTyper-GJB2 assay for detection of GJB2 gene mutations. J Mol Diagn. 16:573–583. 2014. View Article : Google Scholar : PubMed/NCBI
25	Kent A, Turner MA, Sharland M and Heath PT: Aminoglycoside toxicity in neonates: Something to worry about? Expert Rev Anti Infect Ther. 12:319–331. 2014. View Article : Google Scholar : PubMed/NCBI