4305例新生儿遗传性耳聋基因突变携带率及其基因突变位点分析
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摘要
目的了解深圳地区新生儿先天性耳聋基因突变携带率及基因突变类型,为本地区开展大规模耳聋基因筛查提供科学依据。方法采集2016年8月～2018年3月在深圳市龙华区人民医院妇产中心出生的4305名新生儿足跟血,采用基质辅助激光解吸附电离飞行时间质谱技术(MatrixAssistedLaserDesorption/ionizationTime-of-flightMass Spectrometry,MALDI-TOF-MS)对GJB2、SLC26A4、GJB3和线粒体12SrRNA等4个常见耳聋基因的20个热点突变位点进行检测,并对结果进行统计分析。结果 4305例新生儿中检出遗传性耳聋基因突变212例,携带率为4.92%(212/4305),其中男性5.72%(119/2081),高于女性的4.18%(93/2224),差异有统计学意义(χ2=3.405,P<0.05)。GJB2基因突变113例,突变率为53.30%(113/212),明显高于SLC26A4的29.25%(62/212)、GJB3的9.91%(21/212)、线粒体12SrRNA的4.25%(9/212)及复合基因位点突变的3.30%(7/212),差异有统计学意义(χ2=2.815-13.026,P<0.05)。其中基因突变位点频率最高的为GJB2基因的235delC杂合突变,突变率为42.92%(91/212),其次为SLC26A4基因的IVS7-2A>G和GJB3基因的547G>A杂合突变,突变率分别为26.42%(56/212)和7.08%(15/212)。复合基因位点突变主要见于GJB2基因突变位点235delC结合其它位点杂合突变。结论深圳地区新生儿有一定遗传性耳聋常见基因突变携带率,且男性高于女性,主要见于GJB2和SLC26A4基因,突变位点以235delC和IVS7-2A>G杂合突变为主。因此,加强新生儿耳聋基因初筛,对及时治疗和预防耳聋具有重要意义。
Objective:To study the genetic mutation carrying rate and gene mutation type of congenital deafness in shenzhen,It provides scientific basis for large-scale genetic screening of deafness in this region.Methods:Collected heel blood of 4305 infants in shenzhen longhua district people's hospital maternity center born in August 2016 to March 2018,using matrix assisted laser desorption/ionization time-of-flight mass spectrometry of GJB2,SLC26A4,GJB3 and mitochondrial 12 srrna four common deafness gene tested 20 hot spot mutations,and the results were analyzed.Results:Among 4305 newborns,212 cases of genetic deafness gene mutation were detected,carrying rate was 4.92%(212/4305),males was 5.72%(119/2081),higher than females 4.18%(93/2224),the difference was statistically significant(χ2=3.405,P<0.05).113 cases of GJB2 gene mutation were detected,the mutation rate was 53.30%(113/212),significantly higher than the 29.25%(62/212)of SLC26A4,9.91%(21/212)of GJB3,4.25%(9/212)of mitochondrial 12 srrna and 3.30%(7/212)of compound gene locus mutation,the difference was statistically significant(χ2=2.815～2.815,P<0.05).One of the highest frequency of gene mutations in 235 delC of GJB2 hybrid gene mutations,mutation rate was42.92%(91/212),followed by the IVS7-2A>G of SLC26A4 gene and 547G>A of GJB3 gene hybrid gene mutations,The mutation rates were26.42%(56/212)和7.08%(15/212),respectively.The complex gene site mutations are mainly seen in the GJB2 gene mutation site 235 delC binding to other site heterozygous mutations.Conclusion:There is a certain genetic mutation carrying rate of common gene mutation in newborns in shenzhen,and males are higher than females,mainly in GJB2 and SLC26A4 genes,with 235de1 C and ivs7-2A>G heterozygous mutations.Therefore,it is of great significance to strengthen the screening of newborn deafness gene in the timely treatment and prevention of deafness.
Objective:To study the genetic mutation carrying rate and gene mutation type of congenital deafness in shenzhen,It provides scientific basis for large-scale genetic screening of deafness in this region.Methods:Collected heel blood of 4305 infants in shenzhen longhua district people's hospital maternity center born in August 2016 to March 2018,using matrix assisted laser desorption/ionization time-of-flight mass spectrometry of GJB2,SLC26A4,GJB3 and mitochondrial 12 srrna four common deafness gene tested 20 hot spot mutations,and the results were analyzed.Results:Among 4305 newborns,212 cases of genetic deafness gene mutation were detected,carrying rate was 4.92%(212/4305),males was 5.72%(119/2081),higher than females 4.18%(93/2224),the difference was statistically significant(χ2=3.405,P<0.05).113 cases of GJB2 gene mutation were detected,the mutation rate was 53.30%(113/212),significantly higher than the 29.25%(62/212)of SLC26A4,9.91%(21/212)of GJB3,4.25%(9/212)of mitochondrial 12 srrna and 3.30%(7/212)of compound gene locus mutation,the difference was statistically significant(χ2=2.815～2.815,P<0.05).One of the highest frequency of gene mutations in 235 delC of GJB2 hybrid gene mutations,mutation rate was42.92%(91/212),followed by the IVS7-2A>G of SLC26A4 gene and 547G>A of GJB3 gene hybrid gene mutations,The mutation rates were26.42%(56/212)和7.08%(15/212),respectively.The complex gene site mutations are mainly seen in the GJB2 gene mutation site 235 delC binding to other site heterozygous mutations.Conclusion:There is a certain genetic mutation carrying rate of common gene mutation in newborns in shenzhen,and males are higher than females,mainly in GJB2 and SLC26A4 genes,with 235de1 C and ivs7-2A>G heterozygous mutations.Therefore,it is of great significance to strengthen the screening of newborn deafness gene in the timely treatment and prevention of deafness.
引文
[1]王敏,梅瑾,王吴.1398例新生儿脐带血遗传性耳聋基因的筛查分析[J].中国优生与遗传杂志,2017,25(1):34-35,33.
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[3]牟书瑜,刘琳,崔玲,等.大连地区耳聋人群常见聋病基因突变的研究[J].大连医科大学学报,2015,(1):34-36.
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[5]梁鹏飞,王淑娟,王剑,等.陕西省800例非综合征型聋患者常见致聋基因突变分析[J].听力学及言语疾病杂志,2015,23(1):11-15.
[6]李振安,余凤慈,包永新,等.佛山市40672例新生儿耳聋基因筛查结果分析[J].妇产与遗传(电子版),2017,7(1):47-50.
[7]杨晶群,余红,刘丹.绍兴地区7172例新生儿耳聋基因突变位点分析[J].中国优生与遗传杂志,2017,25(5):96-97.
[8]蒋琦,忻蓉,沈学萍,等.2029例新生儿耳聋易感基因筛查结果分析[J].中国妇幼保健杂志,2016,24(5):509-511.
[9]Chan DK,Chang KW.GJB2-associated hearing loss:systematic review of worldwide prevalence,genotype,and auditory phenotype[J].Laryngoscope,2014,124(2):E34-53.
[10]张丽,刘起展,周东.新生儿耳聋基因筛查及分析[J].国外医学医学地理分册,2016,37(4):324-328.
[11]Lu YJ,Yao J,Wei QJ,et al.Diagnostic value of SLC26A4mutation status in hereditary hearing loss with EVA:A PRISMA-Compliant meta-analysis[J].Medicine(Baltimore),2015,94(50):e2248.
[12]陈丁莉,李守霞,要跟东,等.邯郸地区新生儿听力与药物性耳聋易感基因突变联合筛查研究[J].临床儿科杂志,2013,31(2):137-140.
[13]周怡,刘海红,郝津生.15343例新生儿耳聋基因普遍筛查结果分析[J].中国听力语言康复学杂志,2014,12(2):109-112.
[14]李守霞,陈丁莉,张小芳,等.邯郸地区新生儿Gm2和GJB3基因大规模突变筛查[J].中国妇幼保健,2014,29(3):409-412.
[15]赵晓丽,李娇,杨慧芳,等.长治地区耳聋患者常见耳聋基因GJB2、GJB3和线粒体DNA 12S rRNA 1555A>G相关性分析[J].中国优生与遗传杂志,2014,22(8):15-16.
[16]高薇薇,卢文翔,张雷,等.宁波地区非综合征型耳聋患儿耳聋基因热点突变筛查分析[J].浙江医学,2017,39(12):957-960.
[17]杨雪,王幼勤,郭洪源,等.贵州省356例非综合征型聋患者常见致聋基因突变分析[J].听力学及言语疾病杂志,2017,25(1):9-13.
[18]刘水霞,胥亮,陈柏文,等.广西地区127例非综合征性聋患者常见致聋基因突变位点的筛查分析[J].临床耳鼻咽喉头颈外科杂志,2015,29(22):1954-1958.
[2]刘光明,葛菲,杨红.3122例新生儿耳聋基因筛查结果分析[J].中国优生与遗传杂志,2017,25(7):105-106.
[3]牟书瑜,刘琳,崔玲,等.大连地区耳聋人群常见聋病基因突变的研究[J].大连医科大学学报,2015,(1):34-36.
[4]Olney RS,Botto LD.Newborn screening for critical congenital heart disease:essential public health roles for birth defects monitoring programs[J].Birth Defects Res A Clin Mol Teratol,2012,94(12):965-969.
[5]梁鹏飞,王淑娟,王剑,等.陕西省800例非综合征型聋患者常见致聋基因突变分析[J].听力学及言语疾病杂志,2015,23(1):11-15.
[6]李振安,余凤慈,包永新,等.佛山市40672例新生儿耳聋基因筛查结果分析[J].妇产与遗传(电子版),2017,7(1):47-50.
[7]杨晶群,余红,刘丹.绍兴地区7172例新生儿耳聋基因突变位点分析[J].中国优生与遗传杂志,2017,25(5):96-97.
[8]蒋琦,忻蓉,沈学萍,等.2029例新生儿耳聋易感基因筛查结果分析[J].中国妇幼保健杂志,2016,24(5):509-511.
[9]Chan DK,Chang KW.GJB2-associated hearing loss:systematic review of worldwide prevalence,genotype,and auditory phenotype[J].Laryngoscope,2014,124(2):E34-53.
[10]张丽,刘起展,周东.新生儿耳聋基因筛查及分析[J].国外医学医学地理分册,2016,37(4):324-328.
[11]Lu YJ,Yao J,Wei QJ,et al.Diagnostic value of SLC26A4mutation status in hereditary hearing loss with EVA:A PRISMA-Compliant meta-analysis[J].Medicine(Baltimore),2015,94(50):e2248.
[12]陈丁莉,李守霞,要跟东,等.邯郸地区新生儿听力与药物性耳聋易感基因突变联合筛查研究[J].临床儿科杂志,2013,31(2):137-140.
[13]周怡,刘海红,郝津生.15343例新生儿耳聋基因普遍筛查结果分析[J].中国听力语言康复学杂志,2014,12(2):109-112.
[14]李守霞,陈丁莉,张小芳,等.邯郸地区新生儿Gm2和GJB3基因大规模突变筛查[J].中国妇幼保健,2014,29(3):409-412.
[15]赵晓丽,李娇,杨慧芳,等.长治地区耳聋患者常见耳聋基因GJB2、GJB3和线粒体DNA 12S rRNA 1555A>G相关性分析[J].中国优生与遗传杂志,2014,22(8):15-16.
[16]高薇薇,卢文翔,张雷,等.宁波地区非综合征型耳聋患儿耳聋基因热点突变筛查分析[J].浙江医学,2017,39(12):957-960.
[17]杨雪,王幼勤,郭洪源,等.贵州省356例非综合征型聋患者常见致聋基因突变分析[J].听力学及言语疾病杂志,2017,25(1):9-13.
[18]刘水霞,胥亮,陈柏文,等.广西地区127例非综合征性聋患者常见致聋基因突变位点的筛查分析[J].临床耳鼻咽喉头颈外科杂志,2015,29(22):1954-1958.
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