粤东地区1430例新生儿遗传性耳聋基因筛查结果分析
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摘要
目的分析粤东地区遗传性耳聋基因突变类型及突变携带率,为早期发现新生儿耳聋和早期干预提供参考。方法运用PCR结合导流杂交法(耳聋易感基因检测试剂盒)检测粤东地区1 430例新生儿4个遗传性耳聋基因(GJB2、SLC26A4、线粒体DNA、GJB3基因)的13个常见突变位点。查阅广东地区发表的耳聋基因筛查相关文献,分析本地区耳聋基因的流行概况。结果 1 430例新生儿中,检出耳聋基因突变的55例,总阳性率为3.85%,其中GJB2、SLC26A4、GJB3和线粒体DNA耳聋基因的突变率依次为1.61%、1.33%、0.42%和0.28%。检出最多是GJB2 235del和SLC26A4 IVS7-2A>G位点的突变,单基因检出率分别为1.40%和1.05%。双基因突变检出3例,其中GJB2 235delC/SLC26A4 IVS7-2复合杂合突变2例,GJB2 176del16/SLC26A4 IVS7-2复合杂合突变1例;根据文献报道显示,广东其他地区4个耳聋基因的总突变率为3.31%～4.47%,最常见的突变位点是GJB2 235delC和SLC26A4 IVS7-2A>G,其次是GJB2 299delAT和线粒体DNA 1555A>G。结论粤东地区新生儿耳聋基因突变情况与广东其他地区的基本一致,主要的突变类型为GJB2 235delC和SLC26A4 IVS7-2A>G。
Objective To analyze the mutation types of deafness genes in eastern Guangdong newborns and the mutation carrying rate to provide valuable reference for early diagnosis and intervention. Methods PCR combined with flow-through hybridization(Deafness Gene Mutation Detection Array Kit) was used to detect 13 mutation sites of the 4 most common deafness genes(GJB2, SLC26 A4, mtDNA and GJB3) of 1 430 newborns in eastern Guangdong. The literature related to deafness gene screening published in Guangdong was accessed. The prevalence of deafness gene in Guangdong province was analyzed. Results Among 1430 newborns, 55 newborns were detected to have deafness gene mutation, and the total positive rate was 3.85%. The mutation rate of GJB2, SLC26 A4, GJB3 and mtDNA was 1.61%, 1.33%, 0.42% and 0.28%, respectively.The mutations detected the most were those at IVS7-2 A>G site of GJB2 235 del and SLC26 A4, and the detection rate of single gene was 1.40% and 1.05%, respectively. 3 cases were detected to have double-gene mutation, of which there were 2 cases of GJB2 235 delC/SLC26 A4 IVS7-2 mutations and 1 case of GJB2 176 del16/SLC26 A4 IVS7-2 mutation. Literature report showed that the total positive rate of 4 deafness genes was 3.31%-4.47%, and the most common mutations sites were GJB2235 delC and SLC26 A4 IVS7-2 A>G, followed by GJB2 299 delAT and mtDNA 1555 A>G. Conclusion The common deafness genes mutations in newborns in eastern Guangdong is consistent with that in other regions of Guangdong, and the most common mutations were GJB2 235 delC and SLC26 A4 IVS7-2 A>G.
Objective To analyze the mutation types of deafness genes in eastern Guangdong newborns and the mutation carrying rate to provide valuable reference for early diagnosis and intervention. Methods PCR combined with flow-through hybridization(Deafness Gene Mutation Detection Array Kit) was used to detect 13 mutation sites of the 4 most common deafness genes(GJB2, SLC26 A4, mtDNA and GJB3) of 1 430 newborns in eastern Guangdong. The literature related to deafness gene screening published in Guangdong was accessed. The prevalence of deafness gene in Guangdong province was analyzed. Results Among 1430 newborns, 55 newborns were detected to have deafness gene mutation, and the total positive rate was 3.85%. The mutation rate of GJB2, SLC26 A4, GJB3 and mtDNA was 1.61%, 1.33%, 0.42% and 0.28%, respectively.The mutations detected the most were those at IVS7-2 A>G site of GJB2 235 del and SLC26 A4, and the detection rate of single gene was 1.40% and 1.05%, respectively. 3 cases were detected to have double-gene mutation, of which there were 2 cases of GJB2 235 delC/SLC26 A4 IVS7-2 mutations and 1 case of GJB2 176 del16/SLC26 A4 IVS7-2 mutation. Literature report showed that the total positive rate of 4 deafness genes was 3.31%-4.47%, and the most common mutations sites were GJB2235 delC and SLC26 A4 IVS7-2 A>G, followed by GJB2 299 delAT and mtDNA 1555 A>G. Conclusion The common deafness genes mutations in newborns in eastern Guangdong is consistent with that in other regions of Guangdong, and the most common mutations were GJB2 235 delC and SLC26 A4 IVS7-2 A>G.
引文
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[13]唐佳,曾钦龙,李秋丽,等.广东江门地区13725例新生儿遗传性耳聋基因筛查结果分析[J].分子诊断与治疗杂志,2018,10(4):222-227.
[14]孙莉莉,张丽,柳爱华.耳聋基因诊断及其在遗传性耳聋预防和阻断中的应用研究[J].中国产前诊断杂志(电子版),2011,3(2):32-36.
[15]韩冰,李倩,纵亮,等.新生儿听力及基因联合筛查临床实践及筛查模式研究[J].中华耳科学杂志,2013,11(3):380-382.
[16]李振安,梁淑贞,余凤慈,等.佛山市10238例新生儿听力与耳聋易感基因联合筛查分析[J].听力学及言语疾病杂志,2014,22(6):585-588.
[17]周学军,欧阳小梅,刘学忠.常见遗传性聋致病基因研究进展及基因诊断的临床应用[J].听力学及言语疾病杂志,2011,19(1):73-77.
[18]LU Y J,YAO J,WEI Q J,et al.Diagnostic value of SLC26A4 mutation status in hereditary hearing loss with EVA:PRISMA-Compliant meta-analysis[J].Medicine(Baltimore),2015,94(50):e2248.
[19]XIA J H,LIU C Y,TANG B S,et al.Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment[J].Nat Genet,1999,20(4):370-373.
[20]FREI K,RAMSEBNER R,HAMADER G,et al.Lack of association between Connexin 31(GJB3)alterations and sensorineural deafness in Austria[J].Hear Res,2004,194(1-2):81-86.
[21]WANG Q J,LI Q Z,HAN D,et al.Clinical and molecular analysis of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss associated with the mitochondrial 12S rRNA C1494Tmutation[J].Biochem Biophys Res Commun,2006,340(2):583-588.
[2]WILLEMS P J.Genetic causes of hearing loss[J].N Engl JMed,2000,342(15):1101-1109.
[3]韩德民.新生儿听力及耳聋基因联合筛查[J].中国医学文摘(耳鼻咽喉科学),2012,27(6):290-292.
[4]中华人民共和国卫生部.中国出生缺陷防治报告[R].北京:中华人民共和国卫生部,2012.
[5]刘丽益,李维,韩璐好,等.深圳市南山区25 987例新生儿耳聋基因筛查结果分析[J].中国优生与遗传杂志,2018,26(3):75-77.
[6]王世媛,孙晓勉,陆洋,等.新生儿听力与聋病易感基因联合筛查模式探讨[J].中国妇幼健康研究,2017,28(2):156-159.
[7]巫静帆,李小霞,谭淑娟,等.东莞户籍33 810例新生儿听力筛查联合耳聋基因检测与分析[J].中华耳科学杂志,2018,16(2):176-180.
[8]潘丽,苏文,林道彬.珠海地区9 775例新生儿常见耳聋基因突变筛查结果分析[J].广东医学,2017,38(17):2684-2687.
[9]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,2017,7(1):47-50.
[10]刘畅,张彦,杨杰,等.新生儿听力筛查联合聋病易感基因检测的临床应用价值[J].中华实用诊断与治疗杂志,2017,31(9):884-886.
[11]陈文强,熊怡.遗传性耳聋基因筛查对迟发性耳聋的预防作用分析[J].中国医学创新,2018,15(3):120-122.
[12]张艳芳,谢丰华,李闪闪,等.中山市4370例新生儿耳聋基因筛查联合听力筛查结果分析[J].检验医学与临床,2018,15(17):2538-2541.
[13]唐佳,曾钦龙,李秋丽,等.广东江门地区13725例新生儿遗传性耳聋基因筛查结果分析[J].分子诊断与治疗杂志,2018,10(4):222-227.
[14]孙莉莉,张丽,柳爱华.耳聋基因诊断及其在遗传性耳聋预防和阻断中的应用研究[J].中国产前诊断杂志(电子版),2011,3(2):32-36.
[15]韩冰,李倩,纵亮,等.新生儿听力及基因联合筛查临床实践及筛查模式研究[J].中华耳科学杂志,2013,11(3):380-382.
[16]李振安,梁淑贞,余凤慈,等.佛山市10238例新生儿听力与耳聋易感基因联合筛查分析[J].听力学及言语疾病杂志,2014,22(6):585-588.
[17]周学军,欧阳小梅,刘学忠.常见遗传性聋致病基因研究进展及基因诊断的临床应用[J].听力学及言语疾病杂志,2011,19(1):73-77.
[18]LU Y J,YAO J,WEI Q J,et al.Diagnostic value of SLC26A4 mutation status in hereditary hearing loss with EVA:PRISMA-Compliant meta-analysis[J].Medicine(Baltimore),2015,94(50):e2248.
[19]XIA J H,LIU C Y,TANG B S,et al.Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment[J].Nat Genet,1999,20(4):370-373.
[20]FREI K,RAMSEBNER R,HAMADER G,et al.Lack of association between Connexin 31(GJB3)alterations and sensorineural deafness in Austria[J].Hear Res,2004,194(1-2):81-86.
[21]WANG Q J,LI Q Z,HAN D,et al.Clinical and molecular analysis of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss associated with the mitochondrial 12S rRNA C1494Tmutation[J].Biochem Biophys Res Commun,2006,340(2):583-588.