南京地区耳聋患者常见耳聋基因突变的分析

doi:10.6040/j.issn.1673-3770.0.2019.184

摘要/Abstract

摘要： 目的通过对南京地区重度-极重度感音神经性聋患者进行常见耳聋基因检测,分析该类患者常见致聋基因和各位点发生频率,阐明该地区耳聋的遗传病因学。方法首先对患者进行病史采集、体格检查、高分辨颞骨CT以及临床听力学检查,然后采集128例患者的外周静脉血2~4 mL,对其标本进行4种常见基因21个突变位点的检测。结果 128例患者中,39例(30.47%,39/128)检测到基因突变,其中携带双基因杂合突变1例、携带基因纯合突变14例。30例(23.44%,30/128)患者携带GJB2基因突变,其中 18例(14.06%,18/128)为纯合或复合杂合突变。235delC位点突变检出率为20.31%(26/128),299_300delAT位点突变检出率为4.69%(6/128),176_191del位点突变检出率为3.91%(5/128)。10例(7.81%,10/128)患儿携带SLC26A4基因突变,其中携带纯合和复合杂合突变4 例(3.13%,4/128)。IVS7-2 A>G突变检出率为7.03%。患者未检出线粒体12SrRNA基因和GJB3基因突变。患者中高分辨颞骨CT提示前庭导水管扩大者11例,其中检测出SLC26A4基因纯合或杂合突变10例,二者的吻合率为90.91%(10/11)。结论南京地区重度-极重度感音神经性聋患者中,GJB2基因为最主要的致聋基因,其最常见的突变位点是235delC,其次为SLC26A4基因,最常见的突变位点是IVS7-2 A>G。研究发现SLC26A4基因突变在大前庭水管综合征患者中检出率极高,筛查SLC26A4基因热点突变有助于大前庭水管综合征的诊断,但仍需结合高分辨颞骨CT检查,避免患者漏诊。

关键词: 感音神经性耳聋, 基因突变, 基因检测

Abstract: Objective By detecting the common deafness genes in patients with severe to extremely severe sensorineural hearing loss in Nanjing, we aimed to analyze the spectrum and prevalence of the hot-deafness gene mutations among these patients. Moreover, we aimed to clarify the genetic etiology of deafness in patients with severe to extremely severe sensorineural hearing loss in Nanjing. Methods First, we obtained patient data from deafness etiology questionnaires, physical examination, high-resolution temporal bone computed tomography(CT), and clinical audiological examination. Thereafter, 2-4 mL of peripheral venous blood was collected from 128 patients with severe to extremely severe sensorineural hearing loss and the 21 common mutation sites in GJB2, GJB3, SLC26A4, mtDNA, and 12S rRNA genes were analyzed. Results Among the 128 patients, gene mutation in the analyzed sites were detected in 39 cases(30.47%, 39/128). Two patients showed double gene locus mutations, whereas 14 of them showed homozygous mutations. Thirty(23.44%, 30/128)patients were detected with GJB2 gene mutation. Among them, 18(14.06%, 18/128)patients had homozygous or compound heterozygous GJB2 gene mutations. The rate of 235delC mutation sites was 20.31%(26/128), that of the 299-300delAT mutation site was 4.69%(6/128), and that of the 176-191del mutation site was 3.91%(5/128). Ten(7.81%, 10/128)patients were detected with SLC26A4 gene mutation. Among them, 4(3.13%,4/128)patients were detected with homozygous or compound heterozygous SLC26A4 gene mutation. The rate of IVS7-2 A>G mutation was 7.03%. Mutations of mtDNA 12S rRNA and GJB3 genes were not found in the present study. High-resolution temporal bone CT revealed enlarged vestibular aqueduct in 11 patients, and 10 of them tested positive for SLC26A4 homozygous or heterozygous mutations. The concordance rate between genetic diagnosis and temporal bone CT was 90.91%(10/11). Conclusions GJB2 gene mutation was the most commonly observed mutation in patients with severe to extremely severe sensorineural hearing loss in Nanjing, and the most common mutation site was 235delC. SLC26A4 gene mutation was the second most commonly observed mutation, and the most common mutation site was IVS7-2 A>G. SLC26A4 gene mutation is often found in patients with enlarged vestibular aqueduct syndrome, and mutation in this gene is useful to diagnose the syndrome. However, temporal bone CT can be used to reduce the rate of missed diagnosis in patients with sensorineural hearing loss.

Key words: Sensorineural hearing loss, Gene mutation, Gene detection

中图分类号:

R764.4

徐丽娜,高艳慧,何双八. 南京地区耳聋患者常见耳聋基因突变的分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(6): 45-48.

XU Lina, GAO Yanhui, HE Shuangba. Analysis of common deafness genes for hearing loss in Nanjing[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(6): 45-48.

参考文献

[1] Smith RJ, Bale JF Jr, White KR. Sensorineural hearing loss in children[J]. Lancet, 2005, 365(9462): 879-890. doi:10.1016/S0140-6736(05)71047-3.
[2] Morton CC, Nance WE. Newborn hearing screening: a silent revolution[J]. N Engl J Med, 2006, 354(20): 2151-2164. doi:10.1056/NEJMra050700.
[3] 丁淑琴, 王颖, 胡建国. 皖北地区常见耳聋基因突变位点检测与分析[J]. 蚌埠医学院学报, 2018, 43(3): 385-387. doi:10.13898/j.cnki.issn.1000-2200.2018.03.031. DING Shuqin, WANG Ying, HU Jianguo. Detection and analysis of common gene mutation site of deafness in North area of Anhui[J]. Journal of Bengbu Medical College, 2018, 43(3): 385-387. doi:10.13898/j.cnki.issn.1000-2200.2018.03.031.
[4] 韩冰, 王秋菊. 新生儿听力和基因联合筛查研究现状[J]. 中华耳科学杂志, 2013, 11(2): 309-312. doi:10.3969/j.issn.1672-2922.2013.02.035.
[5] 李海波, 李琼, 李红, 等. 非综合征性聋突变热点的流行病学分析[J]. 临床耳鼻咽喉头颈外科杂志, 2012, 26(13): 589-594. doi:10.13201/j.issn.1001-1781.2012.13.009. LI Haibo, LI Qiong, LI Hong, et al. A literature review of epidemiological studies on mutation hot spots of Chinese population with non-syndromic hearing loss[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2012, 26(13): 589-594. doi:10.13201/j.issn.1001-1781.2012.13.009.
[6] Dai P, Yu F, Han B, et al. GJB2 mutation spectrum in 2, 063 Chinese patients with nonsyndromic hearing impairment[J]. J Transl Med, 2009, 7: 26. doi:10.1186/1479-5876-7-26.
[7] Zheng J, Ying ZB, Cai ZY, et al. GJB2 mutation spectrum and genotype-phenotype correlation in 1067 Han Chinese subjects with non-syndromic hearing loss[J]. PLoS One, 2015, 10(6): e0128691. doi:10.1371/journal.pone.0128691.
[8] Yuan YY, You YW, Huang DL, et al. Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from typical areas in China[J]. J Transl Med, 2009, 7: 79. doi:10.1186/1479-5876-7-79.
[9] 詹悦. 极重度耳聋患儿和特发性突聋患者常见耳聋基因突变的分析[D]. 武汉: 华中科技大学, 2014.
[10] Tekin M, Xia XJ, Erdenetungalag R, et al. GJB2 mutations in Mongolia: complex alleles, low frequency, and reduced fitness of the deaf[J]. Ann Hum Genet, 2010,74(2): 155-164. doi: 10.1111/j.1469-1809.2010.00564.x.
[11] Tsukada K, Nishio S, Usami S, et al. A large cohort study of GJB2 mutations in Japanese hearing loss patients[J]. Clin Genet, 2010, 78(5): 464-470. doi:10.1111/j.1399-0004.2010.01407.x.
[12] Usami S, Nishio SY, Nagano M, et al. Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study[J]. PLoS One, 2012, 7(2): e31276. doi:10.1371/journal.pone.0031276.
[13] Park HJ, Hahn SH, Chun YM, et al. Connexin26 mutations associated with nonsyndromic hearing loss[J]. Laryngoscope, 2000, 110(9): 1535-1538. doi:10.1097/00005537-200009000-00023.
[14] Lee KY, Choi SY, Bae JW, et al. Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients[J]. Int J Pediatr Otorhinolaryngol, 2008, 72(9): 1301-1309. doi:10.1016/j.ijporl.2008.05.007.
[15] Wang YC, Kung CY, Su MC, et al. Mutations of Cx26 gene(GJB2)for prelingual deafness in Taiwan[J]. Eur J Hum Genet, 2002, 10(8): 495-498. doi:10.1038/sj.ejhg.5200838.
[16] Shi GZ, Gong LX, Xu XH, et al. GJB2 gene mutations in newborns with non-syndromic hearing impairment in Northern China[J]. Hear Res, 2004, 197(1/2): 19-23. doi:10.1016/j.heares.2004.06.012.
[17] Chan DK, Chang KW. GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype[J]. Laryngoscope, 2014, 124(2): E34-E53. doi:10.1002/lary.24332.
[18] Khandelwal G, Bhalla S, Khullar M, et al. High frequency of heterozygosity in GJB2 mutations among patients with non-syndromic hearing loss[J]. J Laryngol Otol, 2009, 123(3): 273-277. doi:10.1017/S0022215108002892.
[19] 王强, 尤易文, 张启成. 南通地区150例重度-极重度耳聋患者常见致聋基因突变分析[J]. 临床耳鼻咽喉头颈外科杂志, 2013, 27(7): 366-370. doi:10.13201/j.issn.1001-1781.2013.07.012. WANG Qiang, YOU Yiwen, ZHANG Qicheng. The molecular epidemiology analysis of heavy-profound hearing loss in Nangtong[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2013(7): 366-370. doi:10.13201/j.issn.1001-1781.2013.07.012.
[20] 袁永一, 黄莎莎, 王国建, 等. 27个省市聋校学生基于SLC26A4基因IVS7-2A>G突变的全序列分析[J]. 中华耳科学杂志, 2011, 9(1): 17-23. doi:10.3969/j.issn.1672-2922.2011.01.005. YUAN Yongyi, HUANG Shasha, WANG Guojian, et al. Sequencing analysis of entire SLC26A4 gene with focus on IVS7-2A>G mutation in 2352 patients with moderate to profound SNHL in China[J]. Chinese Journal of Otology, 2011, 9(1): 17-23. doi:10.3969/j.issn.1672-2922.2011.01.005.
[21] World Health Organization. Deafness and hearing loss[M]. Geneva: World Health Organization, 2018.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed