绍兴地区131名耳聋患儿常见致聋基因检测结果分析
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摘要
目的通过对耳聋患儿进行常见耳聋基因检测,了解本地区常见遗传性耳聋基因突变谱及突变频率,为遗传性耳聋的远期预防提供科学依据。方法 2014年1月—2016年12月对2家聋儿康复中心聋儿和经新生儿听力筛查确诊的听力损失患儿共131例,应用飞行时间质谱技术进行4个常见耳聋基因GJB2、线粒体12sr RNA、SLC26A4和GJB3检测,检测位点包含以上4个基因的20个热点突变位点。结果 131例耳聋患儿中检出耳聋基因突变63例,检出率为48.09%,其中纯合突变20例,检出率为15.27%,杂合突变53例,检出率为40.46%。GJB2检出38例,检出率为29.01%,SLC26A4 25例,检出率为19.08%,检出频率最高的是GJB2 235del C位点和SLC26A4的IVS7-2 A>G位点,检出率分别为26.72%和12.98%,未检测出GJB3基因和mt DNA突变。有耳聋家族史患儿中有60.71%检出基因突变,与无耳聋家族史者检出率差异无统计学意义(χ2=0.752,P>0.05)。结论本地区耳聋患儿中常见耳聋基因检出率较高,主要为GJB2、SLC26A4基因突变,线粒体12Sr RNA突变可能不是本地区耳聋患儿的主要致病基因,通过耳聋基因检测有助于明确耳聋病因,对家庭再生育风险评估具有重要意义。
Objective Through detecting the common deafness genes in patients,we discover the mutation chart of the hereditary deafness gene and the mutation frequency in the region in order to provide scientific evidence for deafness prevention. Methods The 20 spot mutations of the common deafness genes of GJB2,SLC26 A4,12 sr RNA and GJB3 were detected by using MALDI-TOF-MS technique for 131 patients from 2 deaf children rehabilitation center and out-patients.Results Sixty-three cases were detected with mutation among 131 patients,and the detection rate was 48. 09%. Twenty cases were homozygous mutation,and the ratio was 15. 27%. 51 cases were heterozygous mutation,and the ratio was38. 93%. Thirty-eight cases were GBJ2 mutation,and the ratio was 29. 01%. Twenty-five cases were SLC25 A4 mutation,and the ratio was 19. 08%. The highest detection frequency spots are GJB2 235 del C spot and IVS7-2 A > G spot from SLC26 A4,and the corresponding detection rates are 26. 72% and 12. 98%. GJB3 gene and mt DNA mutation were not detected. 60. 1% patients with family hereditary deafness was detected,and no statistical significance is discovered compared with detecting ratio of patients without family hereditary deafness( χ2= 0. 752,P > 0. 05). Conclusion The detection rate of the common deafness genes among the patients is relatively high in this region,and the major mutations are GJB2 and SLC26 A4. 12 sr RNA may not be the major pathogenic genes of deafness in this region. Detecting the deafness genes can help determine the cause of deafness,and has significance on the family re-birth risk analysis.
Objective Through detecting the common deafness genes in patients,we discover the mutation chart of the hereditary deafness gene and the mutation frequency in the region in order to provide scientific evidence for deafness prevention. Methods The 20 spot mutations of the common deafness genes of GJB2,SLC26 A4,12 sr RNA and GJB3 were detected by using MALDI-TOF-MS technique for 131 patients from 2 deaf children rehabilitation center and out-patients.Results Sixty-three cases were detected with mutation among 131 patients,and the detection rate was 48. 09%. Twenty cases were homozygous mutation,and the ratio was 15. 27%. 51 cases were heterozygous mutation,and the ratio was38. 93%. Thirty-eight cases were GBJ2 mutation,and the ratio was 29. 01%. Twenty-five cases were SLC25 A4 mutation,and the ratio was 19. 08%. The highest detection frequency spots are GJB2 235 del C spot and IVS7-2 A > G spot from SLC26 A4,and the corresponding detection rates are 26. 72% and 12. 98%. GJB3 gene and mt DNA mutation were not detected. 60. 1% patients with family hereditary deafness was detected,and no statistical significance is discovered compared with detecting ratio of patients without family hereditary deafness( χ2= 0. 752,P > 0. 05). Conclusion The detection rate of the common deafness genes among the patients is relatively high in this region,and the major mutations are GJB2 and SLC26 A4. 12 sr RNA may not be the major pathogenic genes of deafness in this region. Detecting the deafness genes can help determine the cause of deafness,and has significance on the family re-birth risk analysis.
引文
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[2]刘璟,牟书瑜,付敏,等.常见耳聋基因在大连地区语前聋患者与耳聋高危人群中的检测分析[J].听力学及言语疾病杂志,2016,24(6):545-548.
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[6]王屹,陈蕾,刘志忠,等.318例中国汉族非综合征性耳聋患者基因突变谱分析[J].中国康复理论与实践,2016,22(12):1451-1454.
[7]刘闽,胥亮,刘水霞,等.广西地区222例感音神经性聋患者常见耳聋基因筛查结果分析[J].听力学及言语疾病杂志,2017,25(1):5-8.
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[9]丁红珂,尹爱华.非综合征性遗传性耳聋的基因诊断进展[J].中国产前诊断杂志(电子版),2015,7(4):48-53.
[10]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,2015,37(1):34-36.
[11]李晓泽,王金桃,魏魏,等.144例耳聋患者常见遗传性耳聋基因检测[J].中国生育杂志,2015,26(3):269-271.
[12]彭新,关兵,刘新,等.扬州地区117例听力障碍婴幼儿常见致聋基因突变分析[J].中国中西医结合耳鼻咽喉科杂志,2015,23(4):298-300.
[13]周永安,杨慧芳,郝子琪,等.山西省非综合征型耳聋患者常见耳聋基因的检测分析[J].中华医学遗传学杂志,2015,32(3):183-186.
[14]刘闽,刘水霞,胥亮,等.广西壮族135例非综合征性聋常见致病基因的研究[J].中华耳科学杂志,2016,14(5):654-659.
[15]余红,刘丹,杨晶群.2 725名新生儿耳聋基因热点突变的筛查分析[J].中华医学遗传学杂志,2015,32(3):335-338.
[16]陆小梅.非综合征型遗传性耳聋常见基因突变及检测方法的研究进展[J].国际儿科学杂志,2016,43(2):109-112.
[17]石之驎,王沙燕,张阮章.非综合征型感音神经性聋患儿GJB2基因突变分析[J].中国医学创新,2016,13(21):21-24.
[18]许军,叶小磊,陈淑飞,等.先天性非综合征性耳聋患者100例常见耳聋基因分析[J].中国眼耳鼻喉科杂志,2014,14(3):184-186.
[19]Tsukada K,Nishio SY,Hattiri M,et al.Ethnic specific spectrum of GJB2 and SLC26A4 mutations their origin and a literature review[J].Ann Otol Rhinol Laryngol,2015,124 Suppl 1:61S-76S.
[20]方媛,顾茂胜,王传霞,等.基因芯片检测技术与基因测序技术在遗传性耳聋产前诊断中的联合应用[J].山东医药,2015,55(47):107-108.
[21]朱美婵,周枫,王蒙,等.广东省59例大前庭水管综合征患者SLC26A4基因突变及表型分析[J].听力学及言语疾病杂志,2016,24(4):335-339.
[22]秦利涛,王莉,郭梁洁,等.罕见耳聋家系GJB2基因新发突变基因检测和产前基因诊断[J].中华实用诊断与治疗杂志,2016,30(6):556-559.
[2]刘璟,牟书瑜,付敏,等.常见耳聋基因在大连地区语前聋患者与耳聋高危人群中的检测分析[J].听力学及言语疾病杂志,2016,24(6):545-548.
[3]戴桂林,刘彦慧,高宇琳,等.东莞地区婴幼儿先天性耳聋的基因检测结果探析[J].河北医学,2016,22(7):1219-1220.
[4]孙晓勉,陆洋,黄旭丽.深圳市福田区新生儿听力及耳聋基因联合筛查分析[J].中国妇幼健康研究,2015,26(6):1119-1121,1135.
[5]相丽丽,林倩,聂文英,等.济南市部分新生儿听力和耳聋基因联合筛查结果分析[J].中华耳鼻喉科头颈外科杂志,2015,50(5):401-405.
[6]王屹,陈蕾,刘志忠,等.318例中国汉族非综合征性耳聋患者基因突变谱分析[J].中国康复理论与实践,2016,22(12):1451-1454.
[7]刘闽,胥亮,刘水霞,等.广西地区222例感音神经性聋患者常见耳聋基因筛查结果分析[J].听力学及言语疾病杂志,2017,25(1):5-8.
[8]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.
[9]丁红珂,尹爱华.非综合征性遗传性耳聋的基因诊断进展[J].中国产前诊断杂志(电子版),2015,7(4):48-53.
[10]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,2015,37(1):34-36.
[11]李晓泽,王金桃,魏魏,等.144例耳聋患者常见遗传性耳聋基因检测[J].中国生育杂志,2015,26(3):269-271.
[12]彭新,关兵,刘新,等.扬州地区117例听力障碍婴幼儿常见致聋基因突变分析[J].中国中西医结合耳鼻咽喉科杂志,2015,23(4):298-300.
[13]周永安,杨慧芳,郝子琪,等.山西省非综合征型耳聋患者常见耳聋基因的检测分析[J].中华医学遗传学杂志,2015,32(3):183-186.
[14]刘闽,刘水霞,胥亮,等.广西壮族135例非综合征性聋常见致病基因的研究[J].中华耳科学杂志,2016,14(5):654-659.
[15]余红,刘丹,杨晶群.2 725名新生儿耳聋基因热点突变的筛查分析[J].中华医学遗传学杂志,2015,32(3):335-338.
[16]陆小梅.非综合征型遗传性耳聋常见基因突变及检测方法的研究进展[J].国际儿科学杂志,2016,43(2):109-112.
[17]石之驎,王沙燕,张阮章.非综合征型感音神经性聋患儿GJB2基因突变分析[J].中国医学创新,2016,13(21):21-24.
[18]许军,叶小磊,陈淑飞,等.先天性非综合征性耳聋患者100例常见耳聋基因分析[J].中国眼耳鼻喉科杂志,2014,14(3):184-186.
[19]Tsukada K,Nishio SY,Hattiri M,et al.Ethnic specific spectrum of GJB2 and SLC26A4 mutations their origin and a literature review[J].Ann Otol Rhinol Laryngol,2015,124 Suppl 1:61S-76S.
[20]方媛,顾茂胜,王传霞,等.基因芯片检测技术与基因测序技术在遗传性耳聋产前诊断中的联合应用[J].山东医药,2015,55(47):107-108.
[21]朱美婵,周枫,王蒙,等.广东省59例大前庭水管综合征患者SLC26A4基因突变及表型分析[J].听力学及言语疾病杂志,2016,24(4):335-339.
[22]秦利涛,王莉,郭梁洁,等.罕见耳聋家系GJB2基因新发突变基因检测和产前基因诊断[J].中华实用诊断与治疗杂志,2016,30(6):556-559.