4例与GJB2基因相关的遗传性耳聋家系的鉴别诊断

齐科研; 杨锴; 闫有圣; 王一鹏; 阴赪宏

PDF(1713 KB)

武警医学 ›› 2022, Vol. 33 ›› Issue (6) : 497-501.

论著

4例与GJB2基因相关的遗传性耳聋家系的鉴别诊断

齐科研, 杨锴, 闫有圣, 王一鹏, 阴赪宏

作者信息 +

Differential diagnosis of hereditary deafness associated with GJB2 gene in 4 families

QI Keyan, YANG Kai, YAN Yousheng, WANG Yipeng, YIN Chenghong

Author information +

文章历史 +

摘要

目的通过遗传学检测明确4例先天性耳聋家系的致病突变,并加以鉴别,针对性地给出诊疗意见。方法选取2020-05至2022-01于北京妇产医院产前诊断中心遗传咨询门诊就诊的4例先天性耳聋家系。利用耳聋基因芯片、全外显子组测序的实验方法,明确其遗传学致病突变,并提供针对性的咨询意见。结果 4例遗传性耳聋均与GJB2基因相关,但存在不同情况。例1为常染色体显性掌跖角化病伴耳聋,其致病变异c.167T>C属新报道;例2中,夫妻双方分别为MYO7A与GJB2复合杂合突变导致的先天性耳聋,其中妻子携带2个新报道致病变异,即MYO7A: c.1214G>A和MYO7A: c.3545A>G;例3为GJB2复合杂合突变引起的常染色体隐性耳聋;例4为GJB2复合杂合突变导致的迟发性耳聋。结论与GJB2基因相关的先天性耳聋具有较强的临床异质性,遗传检测是对其鉴别诊断的必要手段。

Abstract

Objective To identify the diagnostic variations in 4 families with congenital deafness through genetic testing and to provide the corresponding counseling advice.Methods Four families with congenital deafness who visited our center from May 2020 to Jan 2022 were included. The experimental methods of deafness gene chip and whole exome sequencing (WES) were used to identify genetic pathogenic mutations.Results GJB2 gene was associated with all the four cases of hereditary deafness, but there were different conditions. Case 1 was with autosomal dominant pattern, whose de novo pathogenic variation was C.167T>C, a novelly reported variant. In case 2, both wife and husband had congenital deafness, yet caused by MYO7A and GJB2 compound heterozygous variations respectively; and the wife carried two newly reported pathogenic variants, namely MYO7A: C.1214G>A and MYO7A: c.3545A>G. Case 3 was autosomal recessive deafness caused by GJB2 compound heterozygous variation. Case 4 was late on-set deafness caused by GJB2 compound heterozygous variation.Conclusions GJB2 gene-related congenital deafness has strong clinical heterogeneity, and comprehensive genetic testing is necessary for its differential diagnosis.

导出引用

齐科研, 杨锴, 闫有圣, 王一鹏, 阴赪宏. 4例与GJB2基因相关的遗传性耳聋家系的鉴别诊断[J]. 武警医学. 2022, 33(6): 497-501

QI Keyan, YANG Kai, YAN Yousheng, WANG Yipeng, YIN Chenghong. Differential diagnosis of hereditary deafness associated with GJB2 gene in 4 families[J]. Medical Journal of the Chinese People Armed Police Forces. 2022, 33(6): 497-501

中图分类号： R714.55

参考文献

[1] 第二次全国残疾人抽样调查领导小组, 中华人民共和国国家统计局. 2006年第二次全国残疾人抽样调查主要数据公报[J]. 中国康复理论与实践, 2006, 12: 1013.
[2] Wu C C, Hung C C, Lin S Y, et al. Newborn genetic screening for hearing impairment: a preliminary study at a tertiary center[J]. PLoS One, 2011, 6(7): e22314.
[3] 韩明昱, 楚严, 卢彦平, 等. 孕期女性常见耳聋基因筛查与耳聋出生缺陷干预[J]. 中华耳科学杂志, 2011, 9(3): 289-295.
[4] 胡煜, 孙敬武, 孙家强, 等. 非综合征型聋患者常见耳聋基因突变分析[J]. 中华耳科学杂志, 2013, 11(1): 121-125.
[5] 刘畅, 张彦, 丁红珂, 等. 32497例正常听力孕龄女性耳聋基因携带率与突变谱调查[J]. 分子诊断与治疗杂志, 2017, 9(5): 325-327,340.
[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.
[7] 杨锴, 戚红, 黄莎莎, 等. 孕期遗传性耳聋热点致病基因突变筛查及高风险妊娠的产前诊断[J]. 中华耳鼻咽喉头颈外科杂志, 2018, 53(9): 645-649.
[8] 闻小慧, 戚红, 杨锴, 等. 孕妇人群中常见耳聋基因突变检出率的分析[J]. 中国医科大学学报, 2015, 44(2): 152-155.
[9] 吴皓, 黄治物, 杨涛. 先天性耳聋三级防控体系建设[J].听力学及言语疾病杂志, 2017, 25(1): 1-4.
[10] 戴朴, 于飞, 康东洋, 等. 线粒体DNA1555位点和GJB基因及SLC26A4基因的诊断方法及临床应用[J]. 中华耳鼻咽喉头颈外科杂志, 2005, 40(10): 769-773.
[11] 苏钰, 汤文学, 代志瑶, 等. 目标序列捕获及平行测序在临床耳聋基因诊断中的应用[J]. 中华耳科学杂志, 2014, 12(1): 45-49.
[12] 王国建, 张冠斌, 袁永一, 等. 十五项遗传性耳聋基因突变微阵列诊断芯片的临床应用研究[J]. 中华耳科学杂志, 2014, 12(1): 6-10.
[13] 王秋权, 黄莎莎, 袁永一, 等. 第三代测序技术在遗传性耳聋基因拷贝数变异检测的临床应用[J]. 中华耳科学杂志, 2021, 19(2): 227-231.
[14] 张娜, 蒋刈, 宋立强, 等. 基于胎儿有核红细胞建立遗传性耳聋无创产前诊断的新方法[J]. 中华耳科学杂志, 2021, 19(6): 1003-1007.
[15] Elias L A, Wang D D, Kriegstein A R. Gap junction adhesion is necessary for radial migration in the neocortex[J]. Nature, 2007, 448(7156): 901-907.
[16] Morton C C, Nance W E. Newborn hearing screening -asilent revolution[J]. N Engl J Med, 2006, 354: 2151-2164.
[17] 王利伟, 刘涛, 严江伟, 等. 23个非综合征型耳聋家系GJB2基因突变分析[J]. 中国耳鼻咽喉头颈外科, 2021, 28(3): 153-158.
[18] Yang K, Xu Y C, Hu H Y, et al. Investigation of a novel NTRK1variation causing congenital insensitivity to pain with anhidrosis[J]. Front Genet, 2021, 12: 763467.
[19] Wang K L M, Hakonarson H. ANNOVAR: Functional annotation of genetic variants from next-generation sequencing data[J]. Nucleic Acids Res, 2010, 38: e164.
[20] 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.
[21] Hu H Y, Zhang J, Qiu W, et al. Comprehensive strategy improves the genetic diagnosis of different polycystic kidney diseases[J]. J Cell Mol Med, 2021, 25(13): 6318-6332.
[22] Chang K W. Genetics of hearing loss-nonsyndromic[J]. Otolaryngol Clin North Am, 2015, 48(6): 1063-1072.
[23] Morlé L, Bozon M, Alloisio N, et al. A novel C202F mutation in the connexin26 gene (GJB2) associated with autosomal dominant isolated hearing loss[J]. J Med Genet, 2000, 37(5): 368-370.
[24] Heathcote K, Syrris P, Carter N D, et al. A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis (MIM 148350)[J]. J Med Genet, 2000, 37(1): 50-51.
[25] Geel M, Steensel M A, Küster W, et al. HID and KID syndromes are associated with the same connexin 26 mutation[J]. Br J Dermatol, 2002, 146(6): 938-942.
[26] Kelsell D P, Dunlop J, Stevens H P, et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness[J]. Nature, 1997, 387(6628): 80-83.
[27] Chan D K, Chang K W. GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype[J]. Laryngoscope, 2014, 124(2): e34-53.
[28] Snoeckx R L, Huygen P L, Feldmann D, et al. GJB2 mutations and degree of hearing loss: a multicenter study[J]. Am J Hum Genet, 2005, 77(6): 945-957.
[29] Richard G, Brown N, Ishida-Yamamoto A, et al. Expanding the phenotypic spectrum of Cx26 disorders: Bart-Pumphrey syndrome is caused by a novel missense mutation in GJB2[J]. J Invest Dermatol, 2004, 123(5): 856-863.
[30] Alexandrino F, Sartorato E L, Marques-de-Faria A P, et al. G59S mutation in the GJB2 (connexin 26) gene in a patient with Bart-Pumphrey syndrome[J]. Am J Med Genet A, 2005, 136(3): 282-284.
[31] Chen K, Zhan Y, Wu X, et al. Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I [J]. Int J Pediatr Otorhinolaryngol, 2018, 104: 200-204.
[32] 巫朝霞, 梁丽笙, 袁贵龙, 等. 新生儿GJB2基因c.109G_A纯合突变频率及其外显率研究[J]. 甘肃医药, 2021, 40(10): 921-922.