摘要
目的分析GJB2基因p.V37I(c.109G>A)位点突变儿童的临床听力学特点,探讨p.V37I杂合突变的临床意义,为遗传咨询提供临床依据。方法研究对象为2012年至2018年,于我院儿童听力诊断中心就诊,确诊为c.235delC/p.V37I、c.299delAT/p.V37I及c.176del16/p.V37I复合杂合突变的儿童41人。所有儿童均接受新生儿听力筛查、耳聋基因芯片筛查和GJB2基因全编码区检测;同时接受声导抗、畸变产物耳声发射、听性脑干反应、多频稳态诱发电位和小儿行为测听等听力学检测。结果 41例中,男26例、女15例,平均首诊年龄:5.3±4.0个月。常见基因型为c.235delC/p.V37I复合杂合突变,共25例(61.0%)。新生儿听力筛查通过13例(31.7%),未通过28例(68.3%)。4例通过新生儿听力筛查,之后确诊为轻度听力损失,7例未通过新生儿听力筛查,之后确诊为听力正常。听力诊断正常16例(39.0%),听力损失25例(61.0%),其中,轻度14例(56.0%,14/25)、中度11例(44.0%,11/25)。c.235delC/p.V37I突变儿童,52.0%出现听力损失(13/25),以轻度为主。c.299delAT/p.V37I突变儿童,77.3%(10/13)出现听力损失,以中度为主。结论本组GJB2基因p.V37I杂合突变儿童,基因型以c.235delC/p.V37I为主,约39.0%(16/41)表现为听力正常,61.0%(25/41)出现轻-中度听力损失。4例儿童通过新生儿听力筛查,之后出现听力损失,提示GJB2基因p.V37I突变与迟发性听力损失相关。基因型为c.299delAT/p.V37I的儿童出现听力损失可能性较大,临床应予以重视。
Objective To report audiological characteristics in children with p.V37I compound heterozygous mutations and investigate their clinical significance. Methods Forty one subjects with c.235delC/p.V37I, c.299delAT/p.V37I and c.176del16/p.V37I compound heterozygous mutations were recruited at the Clinical Audiological Center for Children, Beijing Tongren Hospital, from 2012 to 2018. All subjects received universal newborn hearing screening, newborn deafness gene screening and GJB2 gene full coding region detection. In additioni, they received acoustic immittance, auditory brainstem response, auditory steady-state response and pediatric behavior audiometry and other audiological tests. Result The average age of the 41 subjects (14 males and 27 females) at the first visit was 5.3±4.0 months. c.235delC/p.V37I compound heterozygous mutation (the most prevalent mutation) was diagnosed in 25 (61.0%) subjects. Only 13 (31.7%) subjects had passed the newborn hearing screening, of whom 4 were diagnosed with mild hearing loss. Seven subjects who had failed the newborn hearing screening were diagnosed with normal hearing later. A total of 16 (39.0%) subjects were determined to have normal hearing and 25 (61.0%) to have hearing loss. Among the 25 subjects with hearing loss, hearing loss was rated as mild in 14 (56.0%) and moderate in 11 (44.0%). Thirteen (52%) of the 25 subjects with the c.235delC/p.V37I mutation showed mainly mild hearing loss while 10 (77.3%) of the 13 subjects with the c.299delAT/p.V37I mutation showed mainly moderate hearing loss. Conclusion The c.235delC/p.V37I mutation is the most prevalent GJB2 gene mutation found in children with p.V37I heterozygous mutations. In this group, 39.0%(16/41) of these children showed normal hearing and 4 children passed the newborn hearing screening but were later diagnosed with hearing loss, indicating possible delayed-onset hearing loss associated with p.V37I mutations in GJB2. Children with c.299delAT / p.V37I mutation are more likely to have hearing loss, requiring additional attention on this issue in the clinic.
作者
王现蕾
王雪瑶
赵雪雷
程晓华
黄丽辉
WANG Xianlei;WANG Xueyao;ZHAO Xuelei;Cheng Xiaohua;HUANG Lihui(Department of Otolaryngology Head and Neck Surgery,Beijing Tongren Hospital,Capital Medical University,BeijingInstitute of Otolaryngology,Key Laboratory of Otolaryngology Head and Neck Surgery,Ministry of Education,Beijing 100005,China)
出处
《中华耳科学杂志》
CSCD
北大核心
2019年第2期227-233,共7页
Chinese Journal of Otology
基金
国家自然科学基金面上项目(No.81870730)
北京市自然科学基金面上项目(No.7172052)~~
