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

目的分析携带GJB2基因p.V37Ⅰ纯合及复合杂合变异婴儿的听力表型,为临床咨询提供参考。方法回顾性分析东莞地区2018年1月至2021年1月在东莞市新生儿听力障碍诊治中心接受遗传咨询与听力检测的210例(420耳)携带GJB2基因p.V37Ⅰ纯合及复合杂合变异婴儿的临床资料,其中男115例,女95例,总结其听力筛查、诊断及随访结果。结果210例婴儿中,166例(79.05%,166/210)未通过听力初筛,84例(57.14%,84/146)未通过听力复筛,106例(50.48%,106/210)在“两步筛查”中通过听力筛查。55例婴儿因第一次听力学诊断异常接受了第二次听力学诊断与相关医学评估,其中43例(75耳)被诊断为听力异常,阳性检出率为17.86%(75/420),其中,67耳(89.33%,67/75)为轻度听力损失,1例单侧和1例双侧(4%,3/75)为中度听力损失,3例单侧和1例双侧(6.67%,5/75)为重度及以上感音神经性聋。4例中度及以上听力损失患儿完善了Sanger测序分析和内耳MRI或颞骨CT检查,其中1例双侧极重度聋患儿前庭发育畸形,1例左侧重度聋患儿蜗神经发育不良,1例同时携带SLC26A4基因突变的双侧中度传导性听力损失患儿为前庭水管扩大。结论p.V37Ⅰ变异外显率较低,听力表型变异度较大,其中迟发性与渐进性听力损失尤其值得关注。

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.