甘肃省10043例新生儿听力联合聋病易感基因筛查的分子流行病学研究

发布时间：2018-12-24 12:20

【摘要】：目的：本研究以新生儿为研究对象,探讨在新生儿听力筛查中进行聋病易感基因筛查的有效性和可行性,以弥补新生儿听力筛查中发现的不足和局限性,并且倡导在新生儿听力筛查中同步进行聋病易感基因筛查的理念。方法：以2009年11月-2011年4月期间出生于甘肃省14个地州市指定医疗卫生机构的10043名新生儿作为研究对象,进行新生儿听力和基因的同步筛查。新生儿听力初步筛查和复筛均采用筛查型耳声发射(otoacoustic emission,OAE),诊断性筛查采用自动判别听性脑干诱发电位(auto-auditory brainstem response, AABR)。初筛时间正常活产儿为出生后48h～72h内,高危儿在病情稳定后出院前进行检查。未通过筛查的新生儿42天后复查,阳性患儿的诊断性检查在出生后三个月进行。基因筛查采用北京解放军301医院王秋菊等设计的含有听力筛查信息和血样信息的新生儿遗传疾病筛查采样卡(ZL200720103139.4)采集新生儿脐带血。此采样卡可以直接用于线粒体12rRNA、GJB2基因以及SLC26A4基因的聚合酶连扩增反应(polymerase chain reaction, PCR)。对PCR结果的阳性产物测序验证。采用DNA Star软件对测序结果进行比对分析。结果：10043名新生儿中参加听力初筛9786例,初筛率97.4%,未参加初筛257例,其中,提前出院或转院221例,家长拒绝筛查29例,死亡7例。初筛通过8377(85.5%)；未通过1409例(14.4%,其中单耳732例,双耳677例。初筛未通过的1409例新生儿有1129例回院复筛,复筛率为80.1%。复筛通过767例(54.4%),单耳或双耳未通过362例(2.57%),280例未回院复筛,失访率为19.7%。基因筛查参加率为100%。聋病基因筛查结果显示：在10043名新生儿中,一共有2.29%(230/10043)新生儿携带一种或两种等位基因突变或线粒体突变,其中包括119名新生儿携带GJB2基因突变,93名新生儿携带SLC26A4基因突变,以及18名线粒体基因突变。这其中还包括2名新生儿为GJB2基因的纯合突变,1名新生儿携带SLC26A4杂合突变和12S rRNA1555AG均质性突变,2名新生儿携带SLC26A4杂合突变和GJB2基因复合杂合突变。然而,有192例基因携带者通过了听力筛查。结论：通过对听力筛查结果的分析,总体的初筛率为97.4%,达到筛查工作要求的95%以上。基因筛查可以做为听力筛查的重要补充,不但能够弥补听力筛查中存在的局限性,提高聋儿的检出率,而且可以明确病因,通过对先证者分子病因学的诊断,有效的遗传咨询将对其家族成员的耳聋防治具有重要意义。将听力筛查和基因筛查联合应用于早期发现处于语前听力损失或迟发型高危患儿或者是致聋基因的携带者,并结合定期的随诊及监测,是目前最为有力的筛查策略。
[Abstract]:Objective: to investigate the effectiveness and feasibility of gene screening for deafness in neonatal hearing screening in order to make up for the deficiency and limitation found in neonatal hearing screening. And advocate the idea of simultaneous genetic screening for deafness in neonatal hearing screening. Methods: from November 2009 to April 2011, 10043 newborns born in 14 designated medical and health institutions in Gansu Province were selected as study subjects, and their hearing and gene were screened simultaneously. Screening otoacoustic emission (otoacoustic emission,OAE) and automatic discriminant auditory brainstem evoked potential (auto-auditory brainstem response, AABR).) were used in the primary and double screening of newborn hearing. The normal screening time was within 48h~72h after birth, and high-risk infants were examined before discharge after stable condition. 42 days after screening, diagnostic tests were performed at 3 months after birth. The neonatal umbilical cord blood was collected by using the neonatal genetic disease screening sampling card (ZL200720103139.4) which was designed by Wang Qiuju and Wang Qiuju of the 301 Hospital of Beijing people's Liberation Army (PLA), which contained the information of hearing screening and blood samples. This sampling card can be directly used for (polymerase chain reaction, PCR). Amplification of mitochondrial 12rRNA-GJB2 gene and SLC26A4 gene by polymerase chain reaction. The positive products of PCR were sequenced. The results of sequencing were analyzed by DNA Star software. Results: among the 10043 newborns, 9786 cases were selected for hearing screening, the screening rate was 97.4%, and 257 cases were not screened. Among them, 221 cases were discharged early or transferred to hospital, 29 cases were refused screening by parents, and 7 cases died. The primary screen passed 8377 (85.5%), 1409 cases (14.4%) failed, including 732 cases with single ear and 677 cases with double ear. Of the 1409 newborns that failed to pass the primary screening, 1129 were returned to hospital and the screening rate was 80.1%. 767 cases (54.4%) passed the double sieve, 362 cases (2.57%) did not pass the double ear or single ear, and 280 cases did not return to hospital. The rate of missing visit was 19.7%. The rate of participation in genetic screening was 100. Genetic screening for deafness showed that 2.29% (230 / 10043) of 10043 newborns carried one or two allele mutations or mitochondrial mutations, including 119 newborns with GJB2 gene mutations. 93 newborns had SLC26A4 gene mutations and 18 had mitochondrial mutations. Among them, 2 neonates were homozygous mutations of GJB2 gene, 1 neonates carried SLC26A4 heterozygosity mutation and 12s rRNA1555AG homogeneity mutation, 2 neonates carried SLC26A4 heterozygosity mutation and GJB2 gene compound heterozygosity mutation. However, 192 gene carriers passed hearing screening. Conclusion: by analyzing the results of hearing screening, the overall screening rate was 97.4, which reached 95% of the screening requirements. Gene screening can be used as an important supplement to hearing screening. It can not only make up for the limitations of hearing screening and improve the detection rate of deaf children, but also make clear the cause of the hearing, and make a diagnosis of the molecular etiology of the proband. Effective genetic counseling will play an important role in the prevention and treatment of deafness of family members. The combination of hearing screening and gene screening is the most effective screening strategy for early detection of children at high risk of prelingual hearing loss or delayed onset or carriers of deafness genes and regular follow-up and monitoring.
【学位授予单位】：兰州大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R764;R722.1

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