The analysis of gene screening results for common hereditary hearing loss in 2 102 pregnant women in Dali area
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摘要: 目的 通过对大理地区孕17周以内的孕妇开展遗传性聋基因检测，强调孕期基因检测和遗传咨询的重要性。 方法 通过PCR扩增技术，对GJB2、GJB3、SLC26A4和mtDNA等4个耳聋基因的21个突变位点进行检测，并对阳性样本的阳性率、突变率和民族分布进行统计描述性分析。 结果 GJB2和SLC26A4基因的阳性率为1.24%和1.43%，在阳性样本中突变率分别占40.62%和46.88%，GJB3基因的阳性率为0.19%，mtDNA突变基因占0.14%，且全部为mtDNA(Heterozygous)，双阳多基因突变型GJB2/SLC26A4仅为1例，阳性率为0.05%，GJB2 c.235delC位点携带频率最高，占GJB2突变基因的65.38%，占突变基因样本26.56%。 结论 GJB2和SLC26A4为最常见的耳聋基因，且GJB2 c.235delC位点最常见，确认耳聋突变位点有助于防止遗传性耳聋儿童出生，基因诊断、遗传咨询和适当的干预对于缓解先天性问题是至关重要的。Abstract: Objective By conducting genetic testing of hereditary hearing loss in pregnant women within 17 weeks of gestation in Dali areas, the importance of genetic testing and genetic counseling during pregnancy was emphasized. Methods Twenty-one mutation sites of 4 hearing loss genes, including GJB2, GJB3, SLC26A4 and mtDNA, were detected by PCR amplification technology. The positive ratio, mutation ratio and ethnic distribution of positive samples were statistically described. Results The positive ratios of GJB2 and SLC26A4 genes were 1.24% and 1.43%, respectively, with mutation rates of 40.62% and 46.88% in the positive samples, respectively. The positive ratio of GJB3gene was 0.19%, and mtDNA mutation genes accounted for 0.14%, and all of them were mtDNA(Heterozygous). There was only one case of GJB2/SLC26A4 double positive multi-gene mutation, with a positive ratio of 0.05%. The frequency of GJB2 c. 235delC site was the highest, accounting for 65.38% of GJB2 mutation genes and 26.56% of mutation gene samples. Conclusion GJB2 and SLC26A4 are the most common genes of hearing loss, and GJB2 c. 235delC site is the most common mutation site. Identifying the hearing loss mutation site is of great importance to prevent the birth of hereditary hearing loss children, and genetic diagnosis, genetic counseling, and appropriate intervention are crucial to alleviate congenital problems.
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Key words:
- hereditary hearing loss /
- hearing loss /
- gene mutation /
- pregnant woman /
- genetic testing
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表 1 孕妇耳聋基因突变位点的各民族分布
例(%) 基因 突变位点 民族 总计 汉族 白族 彝族 回族 GJB2 c.167delT 2(3.13) 0 0 0 2(3.13) c.176_191del16 2(3.13) 0 0 0 2(3.13) c.235delC 6(9.38) 5(7.80) 6(9.38) 0 17(26.57) c.299_300delAT 0 0 0 0 0 c.35delG 1(1.56) 0 1(1.56) 0 2(3.13) c.508_511dupAACG 0 1(1.56) 1(1.56) 1(1.56) 3(4.68) GJB3 c.538C>T 0 0 0 1(1.56) 1(1.56) c.547G>A 3(4.69) 0 0 0 3(4.68) SLC26A4 c.1174A>T 2(3.13) 1(1.56) 0 0 3(4.68) c.1226G>A 0 0 0 0 0 c.1229C>T 3(4.69) 0 0 0 3(4.68) c.1707+5G>A 2(3.13) 0 0 0 2(3.13) c.1975G>C 4(6.25) 0 0 0 4(6.25) c.2027T>A 4(6.25) 0 0 0 4(6.25) c.2162C>T 2(3.13) 0 0 0 2(3.13) c.2168A>G 2(3.13) 1(1.56) 1(1.56) 0 4(6.25) c.281C>T 2(3.13) 0 0 0 2(3.13) c.589G>A 1(1.56) 0 0 0 1(1.56) c.919-2A>G 2(3.13) 0 3(4.69) 0 5(7.81) mtDNA m.1494C>T 0 0 0 0 0 m.1555A>G 3(4.69) 0 0 0 3(4.68) GJB2/SLC26A4 c.176_191del16/c.919-2A>G 1(1.56) 0 0 0 1(1.56) 合计 42(65.63) 8(12.50) 12(18.75) 2(3.12) 64(100.00) 
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[1] Zheng KF, Lin S, Gao J, et al. Novel compound heterozygous MYO15A splicing variants in autosomal recessive non-syndromic hearing loss[J]. BMC Med Genomics, 2024, 17(1): 4. doi: 10.1186/s12920-023-01777-4
[2] 贺骏, 纳洋, 刘激扬. 携带GJB2或SLC26A4基因单杂合变异新生儿的Sanger测序分析[J]. 中华医学遗传学杂志, 2020, 37(11): 1213-1216. doi: 10.3760/cma.j.cn511374-20200304-00126
[3] 谢璧蔚, 李兰. 耳聋基因GJB2及SLC26A4临床表型研究进展[J]. 国际耳鼻咽喉头颈外科杂志, 2021, 45(6): 333-336. doi: 10.3760/cma.j.issn.1673-4106.2021.06.006
[4] 张拔山, 李婵, 朱梓年, 等. 东莞地区16 182名个体18个耳聋易感基因100个变异位点的测序筛查[J]. 中华医学遗传学杂志, 2020, 37(4): 373-377. doi: 10.3760/cma.j.issn.1003-9406.2020.04.003
[5] Lin YH, Wu PC, Tsai CY, et al. Hearing impairment with monoallelic GJB2 variants: a GJB2 cause or non-GJB2 cause?[J]. 2021, 23(10): 1279-1291.
[6] 李溢铭, 王洪阳, 李丹阳, 等. 听神经病患者中GJB2基因变异分布特征及相关性分析[J]. 临床耳鼻咽喉头颈外科杂志, 2024, 38(1): 23-29. https://lceh.whuhzzs.com/article/doi/10.13201/j.issn.2096-7993.2024.01.004
[7] Falah M, Houshmand M, Balali M, et al. Role of GJB2 and GJB6 in Iranian nonsyndromic hearing impairment: from molecular analysis to literature reviews[J]. Fetal Pediatr Pathol, 2020, 39(1): 1-12. doi: 10.1080/15513815.2019.1627625
[8] Le Nabec A, Collobert M, Le Maréchal C, et al. Whole-genome sequencing improves the diagnosis of DFNB1 monoallelic patients[J]. Genes, 2021, 12(8): 1267. doi: 10.3390/genes12081267
[9] Petrova N, Tebieva I, Kadyshev V, et al. Hereditary etiology of non-syndromic sensorineural hearing loss in the Republic of North Ossetia-Alania[J]. PeerJ, 2023, 11: e14514. doi: 10.7717/peerj.14514
[10] Jiang Y, Huang SS, Zhang Y, et al. Evolutionary origin of pathogenic GJB2 alleles in China[J]. Clin Genet, 2022, 102(4): 305-313. doi: 10.1111/cge.14191
[11] 汪在华, 邵莹, 李隽. GJB2基因p. V37I变异及类型与耳聋致病风险的荟萃分析[J]. 中华医学遗传学杂志, 2022, 39(12): 1313-1318. doi: 10.3760/cma.j.cn51137420220321-00186
[12] Doll J, Vona B, Schnapp L, et al. Genetic spectrum of syndromic and non-syndromic hearing loss in Pakistani families[J]. Genes, 2020, 11(11): 1329. doi: 10.3390/genes11111329
[13] Aliazami F, Farhud D, Zarif-Yeganeh M, et al. Gjb3 gene mutations in non-syndromic hearing loss of Bloch, kurd, and Turkmen ethnicities in Iran[J]. Iran J Public Health, 2020, 49(11): 2128-2135.
[14] Gao YJ, Zhang QL, Zhang SY, et al. A connexin gene(GJB3)mutation in a Chinese family with erythrokeratodermia variabilis, ichthyosis and nonsyndromic hearing loss: case report and mutations update[J]. Front Genet, 2022, 13: 797124. doi: 10.3389/fgene.2022.797124
[15] Zeng XX, Liu ZF, Wang J, et al. Combined hearing screening and genetic screening of deafness among Hakka newborns in China[J]. Int J Pediatr Otorhinolaryngol, 2020, 136: 110120. doi: 10.1016/j.ijporl.2020.110120
[16] Ma DY, Zhang JJ, Luo CY, et al. Genetic counseling for patients with nonsyndromic hearing impairment directed by gene analysis[J]. Mol Med Rep, 2016, 13(3): 1967-1974. doi: 10.3892/mmr.2016.4769
[17] Hu H, Zhou P, Wu JY, et al. Genetic testing involving 100 common mutations for antenatal diagnosis of hereditary hearing loss in Chongqing, China[J]. Medicine, 2021, 100(17): e25647. doi: 10.1097/MD.0000000000025647
[18] 陈芳, 张勤颖, 张秋静, 等. 合并感音神经性耳聋的遗传性内分泌代谢病研究进展[J]. 临床耳鼻咽喉头颈外科杂志, 2024, 38(1): 63-69.
[19] Gong YY, Xiong L, Li XJ, et al. A novel mutation of WFS1 gene leading to increase ER stress and cell apoptosis is associated an autosomal dominant form of Wolfram syndrome type 1[J]. BMC Endocr Disord, 2021, 21(1): 76. doi: 10.1186/s12902-021-00748-z
[20] Chou CW, Hsu YC. Current development of patient-specific induced pluripotent stem cells harbouring mitochondrial gene mutations and their applications in the treatment of sensorineural hearing loss[J]. Hear Res, 2023, 429: 108689. doi: 10.1016/j.heares.2023.108689
[21] Wu J, Hao ZJ, Fu DG, et al. Mitochondrial mutations associated with aminoglycoside ototoxicity and hearing loss susceptibility identified by meta-analysis[J]. J Med Genet, 2015, 52(2): 95-103. doi: 10.1136/jmedgenet-2014-102753
[22] Wang JH, Yan DD, Cui HY, et al. Identification of eight genomic protective alleles for mitochondrial diabetes by Kinship-graph convolutional network[J]. J Diabetes Investig, 2024, 15(1): 52-62. doi: 10.1111/jdi.14125
[23] 雷洁, 韩璐好, 邓茜, 等. 33 911例新生儿听力联合耳聋基因筛查及随访结果的分析[J]. 中华医学遗传学杂志, 2021, 38(1): 32-36. doi: 10.3760/cma.j.cn511374-20200322-00189
[24] Han MY, Li ZF, Wang WL, et al. A quantitative cSMART assay for noninvasive prenatal screening of autosomal recessive nonsyndromic hearing loss caused by GJB2 and SLC26A4 mutations[J]. Genet Med, 2017, 19(12): 1309-1316. doi: 10.1038/gim.2017.54
[25] 中国耳聋基因筛查与诊断临床多中心研究协作组, 全国防聋治聋技术指导组. 遗传性耳聋基因筛查规范[J]. 中华医学杂志, 2021, 101(2): 97-102. doi: 10.3760/cma.j.cn112137-20201029-02957
[26] 令娜娜, 郭玉芬, 徐百成. 遗传性耳聋的三级预防策略进展[J]. 实用预防医学, 2021, 28(8): 1021-1024, 封3. doi: 10.3969/j.issn.1006-3110.2021.08.035
[27] 王秋菊, 陈晓巍, 翟晓梅, 等. 孕期耳聋基因筛查专家共识[J]. 中华耳科学杂志, 2022, 20(2): 217-221.
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