携带GJB2基因p.V37Ⅰ纯合及复合杂合变异婴儿的听力表型分析
Clinical Hearing Phenotype Analysis of 210 Infants with GJB2 Gene p.V37Ⅰ Homozygous and Complex Heterozygous Mutation
钟梅芳;马秋林;李楚凌;卢炫廷;
1:浙江中医药大学医学技术与信息工程学院
2:东莞市妇幼保健院耳鼻咽喉科东莞市新生儿听力障碍诊治中心
3:东莞市妇幼保健院产前诊断中心
4:广东凯普生物科技股份有限公司
摘要【Abstract】 Objective To investigate the hearing phenotype of GJB2 gene p. V37I homozygous and complex heterozygous mutation carriers, and mainly analyze their baseline hearing status within 1 year after birth.Methods The clinical data of 210 infants (115 males and 95 females) with GJB2 gene p.V37I homozygative and compound heterozygative mutations who received genetic counseling and hearing testing in Dongguan neonatal hearing impairment diagnosis and treatment center from January 2018 to January 2021 were retrospectively analyzed. The hearing screening, diagnosis and follow-up results were summarized. Results Among the 210 infants, 166 (79.05%，166/210) failed the primary screening, 84 (57.14%，84/146)failed the rescreening, and 106 (50.48%，106/210) passed the“two-step screening”. Of the 55 infants who received a second hearing diagnosis and associated medical evaluation due to abnormal first hearing diagnosis, 43 (75 ears) were diagnosed with abnormal hearing, i. e. positive detection rate 17.86% (75/420).Among them, 67 ears (89.33%, 67/75) had mild hearing loss, 1 unilateral and 1 bilateral moderate hearing loss (4%， 3/75), 3 unilateral and 1 bilateral severe or profound hearing loss (6.67%，5/75). There were 4 cases of children with moderate or more severe hearing loss completed Sanger sequencing analysis and inner ear MRI or temporal bone CT examination, including 1 case of bilateral vestibular malformations with profound hearing loss, 1 case of left cochlear nerve dysplasia with severe hearing loss, 1 case carried SLC26A4 gene mutation with bilateral moderate conductive hearing loss with vestibular aqueduct. Conclusion The penetrance rate of p. V37I mutation is low with large hearing phenotypic variation. The late-onset and progressive hearing loss of p.V37I mutation is worth further attention and discussion in the future.
关键词基金项目(Foundation):作者参考文献1 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.
2 Zou Y,Dai QQ,Tao WJ,et al.Suspension array-based deafness genetic screening in 53,033 Chinese newborns identifies high prevalence of 109 G>A in GJB2[J].Int J Pediatr Otorhinolaryngol,2019,126:109630.
3 Oza AM,DiStefano MT,Hemphill SE,et al.Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss[J].Hum Mutat,2018,39(11):1593-1613.
4 吴皓，黄治物.婴幼儿听力损失诊断与干预指南[J].中华耳鼻咽喉头颈外科杂志，2018,53(3):181-188.
5 钟梅芳，洪晓纯，李楚凌.蜗神经发育不良儿童的临床特征分析[J].听力学及言语疾病杂志，2020,28(3):267-272.
6 周怡，刘海红，龙越，等.听力筛查未通过婴儿的中耳功能与ABR、ASSR及DPOAE检测结果的相关性分析[J].听力学及言语疾病杂志，2019,27(2):144-147.
7 Del Castillo FJ,Del Castillo I.DFNB1 non-syndromic hearing impairment:diversity of mutations and associated phenotypes[J].Front Mol Neurosci,2017,10:428.
8 Kelley PM,Harris DJ,Comer BC,et al.Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss[J].Am J Hum Genet,1998,62(4):792-799.
9 Chen K,Zong L,Liu M ,et al.Developing regional genetic counseling for southern Chinese with nonsyndromic hearing impairment:a unique mutational spectrum[J].Transl Med,2014,12(1):64.
10 中国耳聋基因筛查与诊断临床中心研究协作组，全国防聋治聋技术指导组，戴朴，等.遗传性耳聋基因筛查规范[J].中华医学杂志，2021,101(2):97-102.
11 Chen Y,Hu L,Wang X,et al.Characterization of a knock-in mouse model of the homozygous p.V37I variant in GJB2[J].Sci Rep,2016,6(1):33279.
12 Pollak A,Skórka A,Mueller-Malesińska M,et al.M34T and V37I mutations in GJB2 associated hearing impairment:evidence for pathogenicity and reduced penetrance[J].Am J Med Genet A,2007,143A(21):2534-2543.
13 Wu CC,Tsai CH,Hung CC,et al.Newborn genetic screening for hearing impairment:a population-based longitudinal study[J].Genet Med,2017,19(1):6-12.
14 Li L,Lu J,Tao Z,et al.The p.V37I exclusive genotype of GJB2:a genetic risk-indicator of postnatal permanent childhood hearing impairment[J].PLoS One,2012,7(5):e36621.
15 Du Y,Huang L,Cheng X,et al.Analysis of p.V37I com- pound heterozygous mutations in the GJB2 gene in Chinese infants and young children[J].Biosci Trends,2016,10(3):220-226.
16 Huang Y,Yang XL,Chen WX,et al.Prevalence of p.V37I variant of GJB2 among Chinese infants with mild or moderate hearing loss[J].Int J Clin Exp Med,2015,8(11):21674-21678.
17 Kim SY,Park G,Han KH,et al.Prevalence of p.V37I variant of GJB2 in mild or moderate hearing loss in a pediatric population and the interpretation of its pathogenicity[J].PLoS One,2013,8(4):e61592.
18 Chai Y,Chen D,Sun L,et al.The homozygous p.V37I variant of GJB2 is associated with diverse hearing phenotypes[J].Clin Genet,2015,87(4):350-355.