Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2022, Vol. 36 ›› Issue (4): 27-34.doi: 10.6040/j.issn.1673-3770.0.2022.190

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Clinical application of target gene panel testing in genetic diagnosis of deafness

ZHANG Yanhong1, LI Juanjuan1, ZENG Xianhai1, GOU Lingshan2, WANG Zhaoxia1, WEI Jianfang1, MA Fang1, QIU Shuqi1   

  1. 1. Department of Otolaryngology, Longgang E.N.T. Hospital & Shenzhen Key laboratory of E.N.T, Institute of E.N.T, Shenzhen 518172, Guangdong, China;
    2. Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital, Xuzhou 221009, Jiangsu, China
  • Online:2022-07-20 Published:2022-07-11

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Abstract: Objective This study aimed to explore the application of the deafness gene panel in the genetic analysis of patients with hearing loss. Methods The combination of real-time polymerase chain reaction(PCR)and Sanger sequencing was used to identify the 25 mutations of four common deafness genes in 40 deaf patients. Patients with heterozygous mutations, detected via deafness gene sequencing, underwent further single deafness gene sequencing or target gene panel testing. Those with negative real-time PCR results underwent target gene panel testing. The parents of the 16 patients underwent genetic analysis to identify inherited mutations. Results Among the 40 patients, there were eight patients with a homozygous or compound heterozygous mutation in the GJB2 gene and two patients with a single heterozygous mutation, according to the deafness genetic screening. Moreover, one patient had a homozygous mutation, while two had a single heterozygous mutation in the SLC26A4 gene. The four patients with single heterozygous mutations underwent further single deafness gene sequencing or target gene panel testing. Two patients had the compound heterozygous mutation, GJB2 c.235delC/c.610delC or c.235delC/c.109G>A. Meanwhile, two patients had SLC26A4 c.919-2A>G/c.1548_1549insC. Among the 27 patients with negative real-time PCR results, there were four patients with the homozygous mutation, GJB2 c.109G>A, one patient with c.571T>C/c.G109A, one patient with MYO7A c.397dupC/c.3484A>T, one patient with MYO15A c.4779+2T>C/c.5008-2A>G, and one patient with the heterozygous mutation, ACTG1 c.118C>T, based on target gene panel testing. Additionally, there were two patients with the compound heterozygous mutations, CDH23 c.1765G>A/c.6504T>A and c.6049G>A/c.7225-1G>A, respectively. Among the 16 patients, 15 inherited the deafness genetic mutations from their parents, according to the genetic analysis. Conclusion The deafness gene panel improved the genetic diagnostic rate among deaf patients with negative results of hotspot deafness gene mutations.

Key words: Deafness, GJB2 gene, SLC26A4 gene, MYO7A gene, Deafness gene panel

CLC Number: 

  • R764.43
[1] Lieu JEC, Kenna M, Anne S, et al. Hearing loss in children: a review[J]. JAMA, 2020, 324(21): 2195-2205. doi:10.1001/jama.2020.17647.
[2] Alford RL, Arnos KS, Fox M, et al. American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss[J]. Genet Med, 2014, 16(4): 347-355. doi:10.1038/gim.2014.2.
[3] 刘畅, 黄演林, 汪安石, 等. 阶梯式耳聋基因诊断策略及其临床实践[J]. 分子诊断与治疗杂志, 2022, 14(1): 6-9. doi:10.19930/j.cnki.jmdt.2022.01.002. LIU Chang, HUANG Yanlin, WANG Anshi, et al. A step-by-step approach for hearing loss diagnosis and its clinical practice[J]. Journal of Molecular Diagnostics and Therapy, 2022, 14(1): 6-9. doi:10.19930/j.cnki.jmdt.2022.01.002.
[4] 刘学忠, 欧阳小梅, Denise Yan, 等. 中国人群遗传性耳聋研究进展[J]. 中华耳科学杂志, 2006, 4(2): 81-89. doi:10.3969/j.issn.1672-2922.2006.02.001. LIU Xuezhong, OUYANG Xiaomei, Denise Yan, et al. The genetic deafness in Chinese population[J]. Chinese Journal of Otology, 2006, 4(2): 81-89. doi:10.3969/j.issn.1672-2922.2006.02.001.
[5] 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. doi:10.6040/j.issn.1673-3770.0.2019.184. 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.doi:10.6040/j.issn.1673-3770.0.2019.184.
[6] Shang HQ, Yan D, Tayebi N, et al. Targeted next-generation sequencing of a deafness gene panel(MiamiOtoGenes)analysis in families unsuitable for linkage analysis[J]. Biomed Res Int, 2018, 2018: 3103986. doi:10.1155/2018/3103986.
[7] Xie L, Qiu Y, Jin Y, et al. Hearing screening combined with target gene panel testing increased etiological diagnostic yield in deaf children[J]. Neural Plast, 2021, 2021: 6151973. doi:10.1155/2021/6151973.
[8] Boudewyns A, van den Ende J, Sommen M, et al. Role of targeted next generation sequencing in the etiological work-up of congenitally deaf children[J]. Otol Neurotol, 2018, 39(6): 732-738. doi:10.1097/MAO.0000000000001847.
[9] Tropitzsch A, Schade-Mann T, Gamerdinger P, et al. Diagnostic yield of targeted hearing loss gene panel sequencing in a large German cohort with a balanced age distribution from a single diagnostic center: an eight-year study[J]. Ear Hear, 2022, 43(3): 1049-1066. doi:10.1097/AUD.0000000000001159.
[10] Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. doi:10.1038/gim.2015.30.
[11] 王继. 遗传性耳聋的基因研究进展[J]. 医学综述, 2013, 19(3): 442-444. doi:10.3969/j.issn.1006-2084.2013.03.020. WANG Ji. Advances of study in gene of hereditary hearing impairment[J]. Medical Recapitulate, 2013, 19(3): 442-444. doi:10.3969/j.issn.1006-2084.2013.03.020.
[12] 孙菲菲, 胡松群, 唐艳, 等. 高通量基因捕获测序技术在12个耳聋家庭中的应用[J]. 山东大学耳鼻喉眼学报, 2017, 31(5): 45-49. doi:10.6040/j.issn.1673-3770.0.2017.351. SUN Feifei, HU Songqun, TANG Yan, et al. A next-generation sequencing gene panel for molecular diagnosis in twelve Chinese families with non-syndromic sensorineural hearing loss[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2017, 31(5): 45-49.10.6040/j.issn.1673-3770.0.2017.351.
[13] 黄丽丽, 吴玉璘, 林宁, 等. 江苏省部分地区孕前人群耳聋基因微阵列芯片筛查及遗传咨询[J]. 听力学及言语疾病杂志, 2018, 26(6): 590-595. doi:10.3969/j.issn.1006-7299.2018.06.006. HUANG Lili, WU Yulin, LIN Ning, et al. Pre-pregnancy population screening of deafness gene micro-array and genetic consultation in Jiangsu[J]. Journal of Audiology and Speech Pathology, 2018, 26(6): 590-595. doi:10.3969/j.issn.1006-7299.2018.06.006.
[14] 王现蕾, 王雪瑶, 赵雪雷, 等. 儿童GJB2基因p.V37I位点突变与耳聋临床表型的相关性研究[J]. 中华耳科学杂志, 2019, 17(2): 227-233. doi:10.3969/j.issn.1672-2922.2019.02.017. WANG Xianlei, WANG Xueyao, ZHAO Xuelei, et al. Correlation between p.V37I mutation(c.109G & gt;A)in GJB2 and clinical phenotype of hearing loss in children[J]. Chinese Journal of Otology, 2019, 17(2): 227-233. doi:10.3969/j.issn.1672-2922.2019.02.017.
[15] Du YT, Huang LH, Cheng XH, et al. Analysis of p.V37I compound heterozygous mutations in the GJB2 gene in Chinese infants and young children[J]. Biosci Trends, 2016, 10(3): 220-226. doi:10.5582/bst.2016.01096.
[16] Shen J, Oza AM, del Castillo I, et al. Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel[J]. Genet Med, 2019, 21(11): 2442-2452. doi:10.1038/s41436-019-0535-9.
[17] Boucher S, Tai FWJ, Delmaghani S, et al. Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis[J]. Proc Natl Acad Sci USA, 2020, 117(49): 31278-31289. doi:10.1073/pnas.2010782117.
[18] Peddu D, Amin S, Ying YLM. Characterization of sensorineural hearing loss in patients with MYH9-related disease: a systematic review[J]. Otol Neurotol, 2021, 43(3): e298-e308. doi:10.1097/mao.0000000000003450.
[19] Fakin A, Bonnet C, Kurtenbach A, et al. Characteristics of retinitis pigmentosa associated with ADGRV1 and comparison with USH2A in patients from a multicentric usher syndrome study treatrush[J]. Int J Mol Sci, 2021, 22(19): 10352. doi:10.3390/ijms221910352.
[20] Honda K, Griffith AJ. Genetic architecture and phenotypic landscape of SLC26A4-related hearing loss[J]. Hum Genet, 2022, 141(3/4): 455-464. doi:10.1007/s00439-021-02311-1.
[21] Tsukada K, Nishio SY, Hattori M, et al. Ethnic-specific spectrum of GJB2 and SLC26A4 mutations: their origin and a literature review[J]. Ann Otol Rhinol Laryngol, 2015, 124(Suppl 1): 61S-76S. doi:10.1177/0003489415575060.
[22] 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.
[23] Roesch S, Rasp G, Sarikas A, et al. Genetic determinants of non-syndromic enlarged vestibular aqueduct: a review[J]. Audiol Res, 2021, 11(3): 423-442. doi:10.3390/audiolres11030040.
[24] Farjami M, Fathi M, Ghasemi MM, et al. Investigation of MYO15A and MYO7A mutations in Iranian patients with nonsyndromic hearing loss[J]. Fetal Pediatr Pathol, 2021, 40(2): 121-130. doi:10.1080/15513815.2019.1686790.
[25] Zhang J, Guan J, Wang HY, et al. Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss[J]. BMC Med Genet, 2019, 20(1): 60. doi:10.1186/s12881-019-0790-2.
[26] Chen K, Huang B, Sun J, et al. Cochlear implantation outcomes in children with CDH23 mutations-associated hearing loss[J]. Otolaryngol Head Neck Surg, 2021,9:1945998211057427. doi:10.1177/01945998211057427.
[27] Zhang LM, Cheng JL, Zhou Q, et al. Targeted next-generation sequencing identified novel compound heterozygous variants in the CDH23 gene causing usher syndrome type ID in a Chinese patient[J]. Front Genet, 2020, 11: 422. doi:10.3389/fgene.2020.00422.
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