洛阳地区4106例新生儿遗传性耳聋基因的筛查分析
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摘要
目的通过对洛阳地区4106例新生儿的耳聋致病基因进行检测,以了解洛阳地区耳聋基因的突变类型及其突变携带率,为当地大规模开展耳聋基因筛查提供依据。方法收集在洛阳市妇女儿童医疗保健中心分娩的部分(4106例)新生儿的足跟血,制成滤纸干血片,采用PCR与通用芯片相结合的技术,对滤纸干血斑基因组DNA中与遗传性耳聋相关的9个突变位点:GJB2基因突变位点为c. 35 del G、c. 176 del 16、c.235 del C、c.299 del AT;GJB3基因突变位点为c.538C>T;SLC26A4基因突变位点为c.2168 A>G、c.IVS7-2 A>G;12S rRNA突变位点为m.1494 C>T、m.1555 A>G进行检测。结果 4106例新生儿中共检测出突变198例,突变携带率4.82%。其中GJB2突变106例,突变携带率2.58%;GJB3突变16例,突变携带率0.39%;SLC26A4突变61例,突变携带率1.49%;12S rRNA突变11例,突变携带率0.27%。结论常见耳聋基因突变在新生儿中有较高的携带率。洛阳地区GJB2基因235delC突变是最常见的突变方式,其次是SLC26A4基因IVS7-2 A>G突变。在本地区开展新生儿耳聋基因筛查,具有无损伤、家属易接受的优点,对遗传性耳聋基因的早期诊断、早期干预及遗传咨询具有十分重要的意义。
Objective:To screen common mutations of deafness-related genes in 4106 newborns in luoyang in order to determine the carrier rate,types of mutation in luoyang area to provide a basis for local mass screening of deafness-related genes. Methods:Heel blood of 4106 newborns from Luoyang Maternal and Child Health Care Center were collected. Using PCR combined with deafness gene chip kit capable of detecting 9 mutation sites in four deafness-associated genes.Nine hot mutations including GJB2(c. del 35 G,c. 176 del 16,c. 235 del C,c. 299 del AT);GJB3(c.538 C>T); SLC26A4(c.2168 A>G、c.IVS7-2 A>G);12 S rRNA(m.1494 C>T、m.1555 A>G)were detected. Results:Among the 4106 newborns,198(4.82%)were diagnosed with mutations,including 106(2.58%)with GJB2 mutations,16(0.39%)with GJB3 mutations,61(1.49%)with SLC26A4 mutations,11(0.27%)with 12 S rRNA mutations. Conclusion:The deafness-related gene mutations had high detection rate in LuoYang. The mutation of GJB2 235 del C in luoyang area are the most common,followed by the mutation of SLC26A4(IVS7-2 A>G). Newborn screening for deafness-related gene mutations by heel blood has the advantages of no damage and easy accepting for parents. It plays an important role in the early detection,proper management and genetic counse for Hereditary Deafness.
Objective:To screen common mutations of deafness-related genes in 4106 newborns in luoyang in order to determine the carrier rate,types of mutation in luoyang area to provide a basis for local mass screening of deafness-related genes. Methods:Heel blood of 4106 newborns from Luoyang Maternal and Child Health Care Center were collected. Using PCR combined with deafness gene chip kit capable of detecting 9 mutation sites in four deafness-associated genes.Nine hot mutations including GJB2(c. del 35 G,c. 176 del 16,c. 235 del C,c. 299 del AT);GJB3(c.538 C>T); SLC26A4(c.2168 A>G、c.IVS7-2 A>G);12 S rRNA(m.1494 C>T、m.1555 A>G)were detected. Results:Among the 4106 newborns,198(4.82%)were diagnosed with mutations,including 106(2.58%)with GJB2 mutations,16(0.39%)with GJB3 mutations,61(1.49%)with SLC26A4 mutations,11(0.27%)with 12 S rRNA mutations. Conclusion:The deafness-related gene mutations had high detection rate in LuoYang. The mutation of GJB2 235 del C in luoyang area are the most common,followed by the mutation of SLC26A4(IVS7-2 A>G). Newborn screening for deafness-related gene mutations by heel blood has the advantages of no damage and easy accepting for parents. It plays an important role in the early detection,proper management and genetic counse for Hereditary Deafness.
引文
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[11]郭玉芬,刘晓雯,关静,等.西北地区非综合征型耳聋患者GJB2、SLC26A4基因突变的分子流行病学研究[J].听力学及言语疾病杂志,2008,16(4):263-266.
[12]刘艳平,朱庆文,袁永一.单侧前庭导水管扩大研究进展[J].临床耳鼻咽喉头颈外科杂志,2015,29(1):95-98.
[13]袁永一,戴朴,朱庆文,等.1552例重度感音神经性聋患者与SLC26A4基因IVS7-2 A>G突变相关的全序列分析[J].中华耳鼻咽喉头颈外科杂志,2009,44(6):449-454.
[14]赵亮,王宝龙,孙敬武,等.大前庭水管综合征4个家系SLC26A4基因突变分析[J].安徽医科大学学报,2013,48(10):1221-1225.
[15]袁永一,黄莎莎,王国建,等.27个省市聋校学生基于SLC26A4基因IVS7-2 A>G突变的全序列分析[J].中华耳科学杂志,2011,09(1):17-23.
[16]刘新,戴朴,黄德亮,等.线粒体DNA A1555G突变大规模筛查及其预防意义探讨[J].中华医学杂志,2006,86(19):1318-1322.
[17]鲍晓林,郭玉芬,刘晓雯,等.西北地区与东北地区耳聋先证者线粒体DNA 12SrRNA A1555G突变特点分析[J].听力学及言语疾病杂志,2010,18(4):387-388.
[18]李琦,戴朴,方如平,等.线粒体DNA A1555G突变在中国不同发展地区耳聋人群的对比研究[J].中国听力语言康复科学杂志,2009,(4):13-17.
[19]戴朴,刘新,于飞,等.18个省市聋校学生非综合征型聋病分子流行病学研究[J].中华耳科学杂志,2006,4:(1):1-5.
[20]王帅,魏钦俊,范燚,等.耳聋基因GJB3c.538C>T突变致病性效应的初步研究[J].医学分子生物学杂志,2013,10:(1):10-15.
[21]Najmabadi H,Kahrizi K,Genetics of non-syndromic hearing loss in the Middle East[J].Int J Pediatr Otorhinolaryngol.2014,78:(12):2026-2036.
[2]Alford RL,Sutton VR.Nonsyndromic hereditary hearing loss[J].Adv Otorhinolaryngol,2011,70:37-42.
[3]潘拥军,蒋新液,卫雅蓉,等.新生儿听力筛查联合耳聋基因检测的应用[J].中国优生与遗传杂志,2015,23(12):66-68.
[4]李海波,李琼,李红,等.非综合征性聋突变热点的流行病学分析[J].临床耳鼻咽喉头颈外科杂志,2012,26(13):589-594.
[5]余红,刘丹,杨晶群,等.新生儿听力和常见耳聋基因联合筛查的临床实践[J].中国优生与遗传杂志,2015,23(2):77-78.
[6]郑文波,罗建红,郦云,等.中国人语前非综合征性耳聋患者GJB2基因的突变分析[J].中华儿科杂志,2000,38(10):610-613.
[7]王辉兵,于飞,戴朴,等.GJB2结构功能及制病机制研究[J].中华耳科学杂志,2013,11(1):131-137.
[8]凌琴音,李茂清,徐碧红,等.1280例新生儿听力与耳聋基因联合筛查的临床研究[J].中国优生与遗传杂志,2016,24(5):82-85.
[9]Dai P,Yu F,Han B,et al.GJB2 mutations spectrum in 2063Chinese patients with nonsyndromic hearing impairment[J].J Transl Med,2009,7:26.
[10]周怡,刘海红,郝津生,等.15 343例新生儿耳聋基因普遍筛查结果分析[J].中国听力语言康复科学杂志,2014,12(2):109-112.
[11]郭玉芬,刘晓雯,关静,等.西北地区非综合征型耳聋患者GJB2、SLC26A4基因突变的分子流行病学研究[J].听力学及言语疾病杂志,2008,16(4):263-266.
[12]刘艳平,朱庆文,袁永一.单侧前庭导水管扩大研究进展[J].临床耳鼻咽喉头颈外科杂志,2015,29(1):95-98.
[13]袁永一,戴朴,朱庆文,等.1552例重度感音神经性聋患者与SLC26A4基因IVS7-2 A>G突变相关的全序列分析[J].中华耳鼻咽喉头颈外科杂志,2009,44(6):449-454.
[14]赵亮,王宝龙,孙敬武,等.大前庭水管综合征4个家系SLC26A4基因突变分析[J].安徽医科大学学报,2013,48(10):1221-1225.
[15]袁永一,黄莎莎,王国建,等.27个省市聋校学生基于SLC26A4基因IVS7-2 A>G突变的全序列分析[J].中华耳科学杂志,2011,09(1):17-23.
[16]刘新,戴朴,黄德亮,等.线粒体DNA A1555G突变大规模筛查及其预防意义探讨[J].中华医学杂志,2006,86(19):1318-1322.
[17]鲍晓林,郭玉芬,刘晓雯,等.西北地区与东北地区耳聋先证者线粒体DNA 12SrRNA A1555G突变特点分析[J].听力学及言语疾病杂志,2010,18(4):387-388.
[18]李琦,戴朴,方如平,等.线粒体DNA A1555G突变在中国不同发展地区耳聋人群的对比研究[J].中国听力语言康复科学杂志,2009,(4):13-17.
[19]戴朴,刘新,于飞,等.18个省市聋校学生非综合征型聋病分子流行病学研究[J].中华耳科学杂志,2006,4:(1):1-5.
[20]王帅,魏钦俊,范燚,等.耳聋基因GJB3c.538C>T突变致病性效应的初步研究[J].医学分子生物学杂志,2013,10:(1):10-15.
[21]Najmabadi H,Kahrizi K,Genetics of non-syndromic hearing loss in the Middle East[J].Int J Pediatr Otorhinolaryngol.2014,78:(12):2026-2036.