Developing regional genetic counseling for southern Chinese with nonsyndromic hearing impairment: a unique mutational spectrum

Journal of Translational Medicine

Hongyan Jiang¹  Haocheng Tang¹  Chang Dong¹  Hui Cao¹  Yuan Zhan¹  Wei Zhou¹  Xianren Wang¹  Min Liu¹  Ling Zong¹  Kaitian Chen¹ 

[1] Department of Otorhinolaryngology, the First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou 510080, People's Republic of China

关键词: Gene mutation;    WFS1;    GJB3;    Mitochondrial DNA;    SLC26A4;    GJB2;    Non-syndromic hearing impairment;    South China;   

Others  :  817716
DOI  :  10.1186/1479-5876-12-64

 received in 2013-11-20, accepted in 2014-03-03,  发布年份 2014

【 摘 要 】

Background

Racial and regional factors are important for the clinical diagnosis of non-syndromic hearing impairment. Comprehensive genetic analysis of deaf patients in different regions of China must be performed to provide effective genetic counseling. To evaluate the mutational spectrum of south Chinese families, we performed genetic analysis for non-syndromic hearing impairment in this population.

Methods

Complete clinical evaluations were performed on 701 unrelated patients with non-syndromic hearing impairment from six provinces in south China. Each subject was screened for common mutations, including SLC26A4 c.IVS7-2A > G, c.2168A > G; mitochondrial DNA m.1555A > G, m.1494C > T, m.7444G > A, m.7445A > G; GJB3 c.538C > T, c.547G > A; and WFS1 c.1901A > C, using pyrosequencing. GJB2 and SLC26A4 coding region mutation detection were performed using Sanger sequencing.

Results

Genetic analysis revealed that among the etiology of non-syndromic hearing impairment, GJB2, SLC26A4, and mitochondrial m.1555A > G mutations accounted for 18.0%, 13.1%, and 0.9%, respectively. Common mutations included GJB2 c.235delC, c.109G > A, SLC26A4 c.IVS7-2A > G, c.1229 T > C, and mitochondrial m.1555A > G. The total mutation rate was 45.1% in all patients examined in south China. Overall, the clear contribution of GJB2, SLC26A4, and mitochondrial m.1555A > G to the etiology of the non-syndromic deafness population in south China was 32.0%.

Conclusions

Our study is the first genetic analysis of non-syndromic hearing impairment in south China, and revealed that a clear genetic etiology accounted for 32.0% of non-syndromic hearing cases in patients from these regions. The mutational spectrum of non-syndromic hearing impairment in the south Chinese population provides useful and targeted information to aid in genetic counseling.

【 授权许可】

   
2014 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Morton CC, Nance WE: Newborn hearing screening–a silent revolution. N Engl J Med 2006, 354:2151-2164.
• [2]Rabionet R, Zelante L, López-Bigas N, D’Agruma L, Melchionda S, Restagno G, Arbonés ML, Gasparini P, Estivill X: Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene. Hum Genet 2000, 106:40-44.
• [3]Gabriel H, Kupsch P, Sudendey J, Winterhager E, Jahnke K, Lautermann J: Mutations in the connexin26/GJB2 gene are the most common event in non-syndromic hearing loss among the German population. Hum Mutat 2001, 17:521-522.
• [4]Dai P, Yu F, Han B, Wu H, Yuan YY, Li Q, Wang GJ, Liu X, He J, Huang DL, Kang DY, Zhang X, Yuan HJ, Leejun CW, Han DY: Features of nationwide distribution and frequency of a common gap junction beta-2 gene mutation in China. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2007, 42:804-808. in Chinese
• [5]Yuan Y, Zhang X, Huang S, Zuo L, Zhang G, Song Y, Wang G, Wang H, Huang D, Han D, Dai P: Common molecular etiologies are rare in nonsyndromic Tibetan Chinese patients with hearing impairment. PLoS One 2012, 7:e30720.
• [6]Yu F, Han DY, Dai P, Kang DY, Zhang X, Liu X, Zhu QW, Yuan YY, Sun Q, Xue DD, Li M, Liu J, Yuan HJ, Yang WY: Mutation of GJB2 gene in Chinese nonsyndromic hearing impairment patients: analysis of 1190 cases. Nat Med J Chin 2007, 87:2814-2819. in Chinese
• [7]Yuan Y, You Y, Huang D, Cui J, Wang Y, Wang Q, Yu F, Kang D, Yuan H, Han D, Dai P: Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from typical areas in China. J Transl Med 2009, 7:79. BioMed Central Full Text
• [8]Dai P, Yu F, Han B, Liu X, Wang G, Li Q, Yuan Y, Liu X, Huang D, Kang D, Zhang X, Yuan H, Yao K, Hao J, He J, He Y, Wang Y, Ye Q, Yu Y, Lin H, Liu L, Deng W, Zhu X, You Y, Cui J, Hou N, Xu X, Zhang J, Tang L, Song R, et al.: GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment. J Transl Med 2009, 7:1-12. BioMed Central Full Text
• [9]Guo YF, Liu XW, Guan J, Han MK, Wang DY, Zhao YL, Rao SQ, Wang QJ: GJB2, SLC26A4 and mitochondrial DNA A1555G mutations in prelingual deafness in Northern Chinese subjects. Acta Otolaryngol 2008, 128:297-303.
• [10]Chen Y, Tudi M, Sun J, He C, Lu HL, Shang Q, Jiang D, Kuyaxi P, Hu B, Zhang H: Genetic mutations in non-syndromic deafness patients of Uyghur and Han Chinese ethnicities in Xinjiang, China: a comparative study. J Transl Med 2011, 9:154. BioMed Central Full Text
• [11]Xin F, Yuan Y, Deng X, Han M, Wang G, Zhao J, Gao X, Liu J, Yu F, Han D, Dai P: Genetic mutations in nonsyndromic deafness patients of Chinese minority and Han ethnicities in Yunnan, China. J Transl Med 2013, 11:312. BioMed Central Full Text
• [12]Yuan Y, Yu F, Wang G, Huang S, Yu R, Zhang X, Huang D, Han D, Dai P: Prevalence of the GJB2 IVS1 + 1G > A mutation in Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2. J Transl Med 2010, 8:127. BioMed Central Full Text
• [13]Ferraris A, Rappaport E, Santacroce R, Pollak E, Krantz I, Toth S, Lysholm F, Margaglione M, Restagno G, Dallapiccola B, Surrey S, Fortina P: Pyrosequencing for detection of mutations in the connexin 26 (GJB2) and mitochondrial 12S RNA (MTRNR1) genes associated with hereditary hearing loss. Hum Mutat 2002, 4:312-320.
• [14]Chen K, Wang X, Sun L, Jiang H: Screening of SLC26A4, FOXI1, KCNJ10, and GJB2 in bilateral deafness patients with inner ear malformation. Otolaryngol Head Neck Surg 2012, 146(6):972-978.
• [15]Kenneson A, Van Naarden BK, Boyle C: GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review. Genet Med 2002, 4(4):258-274.
• [16]Chen K, Zong L, Zhou W, Liu M, Jiang H: GJB3 and GJB6 genes screening in 200 non-syndromic hearing impairment patients. J Audiology Speech Pathol 2012, 20(3):198-200. in Chinese
• [17]Wu BL, Lindeman N, Lip V, Adams A, Amato RS, Cox G, Irons M, Kenna M, Korf B, Raisen J, Platt O: Effectiveness of sequencing connexin 26 (GJB2) in cases of familial or sporadic childhood deafness referred for molecular diagnostic testing. Genet Med 2002, 4(4):279-288.
• [18]Albert S, Blons H, Jonard L, Feldmann D, Chauvin P, Loundon N, Sergent-Allaoui A, Houang M, Joannard A, Schmerber S, Delobel B, Leman J, Journel H, Catros H, Dollfus H, Eliot MM, David A, Calais C, Drouin-Garraud V, Obstoy MF, Tran Ba Huy P, Lacombe D, Duriez F, Francannet C, Bitoun P, Petit C, Garabédian EN, Couderc R, Marlin S, Denoyelle F: SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Eur J Hum Genet 2006, 6:773-779.
• [19]Yuan YY, Dai P, Zhu QW, Kang DY, Huang DL: Sequencing analysis of whole SLC26A4 gene related to IVS7-2A > G mutation in 1552 moderate to profound sensorineural hearing loss patients in China. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2009, 44(6):449-454. in Chinese
• [20]Zhu Q, Dai P, Han D, Lin H, Yuan Y, Yu F, Liu X, Kang D, Zhang X, Jin Z, Liu L: Analysis of SLC26A4 mutation in the deafness patients from the city of Anyang. J Audiology Speech Pathol 2007, 3:181-183. in Chinese
• [21]Park HJ, Lee SJ, Jin HS, Lee JO, Go SH, Jang HS, Moon SK, Lee SC, Chun YM, Lee HK, Choi JY, Jung SC, Griffith AJ, Koo SK: Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans. Clin Genet 2005, 67(2):160-165.
• [22]Tsukamoto K, Suzuki H, Harada D, Namba A, Abe S, Usami S: Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese. Eur J Hum Genet 2003, 12:916-922.
• [23]Guan MX: Prevalence of mitochondrial 12S rRNA mutations associated with aminoglycoside ototoxicity. Volta Rev 2005, 105:211-227.
• [24]Usami S, Abe S, Akita J, Namba A, Shinkawa H, Ishii M, Iwasaki S, Hoshino T, Ito J, Doi K, Kubo T, Nakagawa T, Komiyama S, Tono T, Komune S: Prevalence of mitochondrial gene mutations among hearing impaired patients. J Med Genet 2000, 37:38-40.
• [25]Malik SG, Pieter N, Sudoyo H, Kadir A, Marzuki S: Prevalence of the mitochondrial DNA A1555G mutation in sensorineural deafness patients in island Southeast Asia. J Hum Genet 2003, 48:480-483.
• [26]Liu XZ, Yuan Y, Yan D, Ding EH, Ouyang XM, Fei Y, Tang W, Yuan H, Chang Q, Du LL, Zhang X, Wang G, Ahmad S, Kang DY, Lin X, Dai P: Digenic inheritance of non-syndromic deafness caused by mutations at the gap junction proteins Cx26 and Cx31. Hum Genet 2009, 125:53-62.
• [27]Li Q, Wang Q, Zhao L, Yuan H, Li L, Liu Q, Han D: Mutation analysis of GJB3 in Chinese population with non-syndromic hearing impairment. J Audiology Speech Pathol 2005, 13(3):145-148. in Chinese
• [28]Yuan Y, Huang D, Dai P, Zhu Q, Liu X, Wang G, Li Q, Wu B: GJB6 gene mutation analysis in Chinese nonsyndromic deaf population. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2007, 21:3-6. in Chinese
• [29]Komatsu K, Nakamura N, Ghadami M, Matsumoto N, Kishino T, Ohta T, Niikawa N, Yoshiura K: Confirmation of genetic homogeneity of nonsyndromic low-frequency sensorineural hearing loss by linkage analysis and a DFNA6/14 mutation in a Japanese family. J Hum Genet 2002, 47:395-399.