甘肅省10043例新生兒聽力聯(lián)合聾病易感基因篩查的分子流行病學(xué)研究
發(fā)布時(shí)間：2018-12-24 12:20
【摘要】：目的：本研究以新生兒為研究對(duì)象,探討在新生兒聽力篩查中進(jìn)行聾病易感基因篩查的有效性和可行性,以彌補(bǔ)新生兒聽力篩查中發(fā)現(xiàn)的不足和局限性,并且倡導(dǎo)在新生兒聽力篩查中同步進(jìn)行聾病易感基因篩查的理念。 方法：以2009年11月-2011年4月期間出生于甘肅省14個(gè)地州市指定醫(yī)療衛(wèi)生機(jī)構(gòu)的10043名新生兒作為研究對(duì)象,進(jìn)行新生兒聽力和基因的同步篩查。新生兒聽力初步篩查和復(fù)篩均采用篩查型耳聲發(fā)射(otoacoustic emission,OAE),診斷性篩查采用自動(dòng)判別聽性腦干誘發(fā)電位(auto-auditory brainstem response, AABR)。初篩時(shí)間正常活產(chǎn)兒為出生后48h～72h內(nèi),高危兒在病情穩(wěn)定后出院前進(jìn)行檢查。未通過篩查的新生兒42天后復(fù)查,陽性患兒的診斷性檢查在出生后三個(gè)月進(jìn)行�；蚝Y查采用北京解放軍301醫(yī)院王秋菊等設(shè)計(jì)的含有聽力篩查信息和血樣信息的新生兒遺傳疾病篩查采樣卡(ZL200720103139.4)采集新生兒臍帶血。此采樣卡可以直接用于線粒體12rRNA、GJB2基因以及SLC26A4基因的聚合酶連擴(kuò)增反應(yīng)(polymerase chain reaction, PCR)。對(duì)PCR結(jié)果的陽性產(chǎn)物測序驗(yàn)證。采用DNA Star軟件對(duì)測序結(jié)果進(jìn)行比對(duì)分析。 結(jié)果：10043名新生兒中參加聽力初篩9786例,初篩率97.4%,未參加初篩257例,其中,提前出院或轉(zhuǎn)院221例,家長拒絕篩查29例,死亡7例。初篩通過8377(85.5%)；未通過1409例(14.4%,其中單耳732例,雙耳677例。初篩未通過的1409例新生兒有1129例回院復(fù)篩,復(fù)篩率為80.1%。復(fù)篩通過767例(54.4%),單耳或雙耳未通過362例(2.57%),280例未回院復(fù)篩,失訪率為19.7%�；蚝Y查參加率為100%。聾病基因篩查結(jié)果顯示：在10043名新生兒中,一共有2.29%(230/10043)新生兒攜帶一種或兩種等位基因突變或線粒體突變,其中包括119名新生兒攜帶GJB2基因突變,93名新生兒攜帶SLC26A4基因突變,以及18名線粒體基因突變。這其中還包括2名新生兒為GJB2基因的純合突變,1名新生兒攜帶SLC26A4雜合突變和12S rRNA1555AG均質(zhì)性突變,2名新生兒攜帶SLC26A4雜合突變和GJB2基因復(fù)合雜合突變。然而,有192例基因攜帶者通過了聽力篩查。 結(jié)論：通過對(duì)聽力篩查結(jié)果的分析,總體的初篩率為97.4%,達(dá)到篩查工作要求的95%以上�；蚝Y查可以做為聽力篩查的重要補(bǔ)充,不但能夠彌補(bǔ)聽力篩查中存在的局限性,提高聾兒的檢出率,而且可以明確病因,通過對(duì)先證者分子病因?qū)W的診斷,有效的遺傳咨詢將對(duì)其家族成員的耳聾防治具有重要意義。將聽力篩查和基因篩查聯(lián)合應(yīng)用于早期發(fā)現(xiàn)處于語前聽力損失或遲發(fā)型高�；純夯蛘呤侵旅@基因的攜帶者,并結(jié)合定期的隨診及監(jiān)測,是目前最為有力的篩查策略。
[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.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R764;R722.1
本文編號(hào)：2390613
[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.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R764;R722.1
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