高危新生儿听力和聋病易感基因联合筛查临床研究

A Clinical Study of Hearing Concurrent Genetic Screening in High-Risk Newborns

摘要: 目的：探讨在高危新生儿听力筛查基础上，联合聋病易感基因筛查的临床意义。方法：随机选择920例新生儿科住院具有听力损失高危因素的新生儿，于生后3~5天采集微量足跟血进行基因GJB2、SLC26A4及线粒体12SrRNA的聚合酶链扩增反应，通过基质辅助激光解吸附/电离飞行时间质谱方法检测GJB2基因35delG、176-191del16、235delC、299-300delAT；SLC26A4基因IVS7-2A > G、2168A > G；线粒体12SrRNA基因1494C > T、1555A > G等3个基因8个突变位点；听力筛查初筛采用自动判别听性脑干电位(auto-auditory brainstem response AABR)，复筛采用诊断型耳声反射(otoacoustic emission OAE) + AABR，仍不通过者于3月龄行听力学诊断；选取同期产后区938例健康新生儿为对照组。结果：高危新生儿组检出35例聋病基因携带，3个基因突变的总体携带率3.80%；检出听力障碍34例(3.70%)、其中重度以上听力障碍15例(1.63%)；30例(85.7%)聋病基因携带者通过了听力筛查。对照组检出21例聋病基因携带，3个基因突变的总体携带率2.23%；检出听力障碍4例(0.43%)、重度以上听力障碍1例(0.11%)；17例(68.0%)聋病基因携带者通过了听力筛查。两组聋病基因突变的总携带率、听力障碍及重度以上听力障碍检出率以及携带聋病基因者听力筛查通过率之间差异有统计学意义。结论：高危新生儿听力障碍的发生率和聋病基因突变携带率均高于正常新生儿应重点关注；采用听力和聋病易感基因联合筛查能及时发现常规通过听力筛查但具有耳聋高危因素和迟发性聋病遗传因素的新生儿，对早期干预、定期随访、减少聋病发生具有指导意义。

Abstract: Objective: To investigate the mutation frequency and types of deafness susceptibility genes (GJB2, 12SrNA, SLC26A4) among high-risk neonates and to discuss the clinic signification of combining the original hearing screening with deafness susceptibility genes screening. Methods: 920 newborns with risk factors of hearing loss in the neonatology ward were chosen to collect films of heel blood for the study. Eight mutations of three genes (GJB2 35delG, 176-191del16, 235delC, 299-300delAT; SLC26A4 IVS7-2A > G, 2168 > G; MT 12SrRNA 1494C > T, 1555A > G) were detected by matrix assister laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Meanwhile, all these newborns received hearing screening. Auto-auditory brainstem response (AABR) was used for the first step screening and otoacoustic emission (OAE) combined with AABR was used for the second step screening. Audiology diagnosis would be applied for those who failed to pass the hearing screening when they were 3 months old. 938 healthy newborns in maternity ward as control group received same screening. Results: 35 infants with risk factors were deafness predisposing gene carriers. The overall carrier frequency of three genes was 3.8%, 34 were diag-nosed as hearing loss (3.7%) and 15 were diagnosed as severe hearing loss (1.63%). 30 (85.7%) carriers of deafness predisposing gene passed the hearing screening. 21 infants were deafness predisposing gene carriers in control group. The overall carrier frequency of three genes was 2.23%, 4 were diagnosed as hearing loss (0.43%) and 1 was diagnosed as severe hearing loss (0.11%). 17 (68%) carriers of deafness predisposing gene passed the hearing screening. Overall carrier frequency of three genes and detection rate of hearing loss or severe hearing loss were significant between the two groups. Conclusion: There were significant differences in carrier frequency of deafness predisposing gene and detection rate of hearing loss or severe hearing loss between the two groups. To combine newborns hearing screening with deafness susceptibility genes screening is able to find the newborns who will pass the regular hearing screening but with high deafness risks and late-onset deafness susceptibility genes. As a result, it is of guiding significance to early intervention, regular follow-up and deafness preventing.