中国西南三区216例儿童葡萄糖-6-磷酸脱氢酶缺乏症基因型分布和临床特征分析
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摘要
目的了解葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症患者基因突变型在四川(川)、云南(滇)、贵州(黔)三地区的分布情况及临床特征,为该病的临床诊治提供实验室依据。方法对来自川滇黔疑似G6PD缺乏症的汉族患者450例(男342例,女108例),采用多色探针荧光PCR熔解曲线法进行G6PD基因型别检测,并分析基因突变类型与临床表型之间的关系。结果 450例可疑样本中,检出215例(男172例,女43例)单基因突变和1例含1388G>A和1004C>A复合型突变。11种单基因突变型所占比例分别为:1388G>A型29.78%;1376G>T型24.65%;1024C>T型22.33%;95A>G型12.09%;871G>A型4.05%;392G>T型2.33%;517T>C型1.39%;487G>T型0.93%;1004C>A型0.93%;1387C>T型0.47%;1360C>T型0.47%。川、滇和黔三地优势基因均为1388G>A、1376G>T和1024C>T型。男女患儿前两位突变位点均为1388G>A(26.7%,41.9%)和1376G>T(26.2%,18.6%), 1024C>T(25.0%)居男性患儿第3位,女性第3位则为95A>G (14.0%)。<1岁的患儿以1024C>T(28.0%)、1388G>A(25.6%)和1376G>T(25.0%)型为主,>1岁的患儿以1388G>A(43.1%)、1376G>T(23.5%)和95A>G(15.7%)为主。男性患儿酶活性明显低于女性患儿,各基因突变型在同一性别之间酶活性差异无统计学意义(F=0.680、1.629,P=0.666、0.177)。肝肿大、贫血、黄疸和尿色改变为主要的临床表现,不同基因型与临床表现之间差异无统计学意义(P>0.05)。结论川、滇、黔三地区汉族人群中G6PD缺乏症患儿基因突变型以1388G>A、1376G>T和1024C>T为优势突变基因,呈多样化分布。突变型可能与性别和首次发病年龄有关,各突变型之间没有明显的临床表现和酶活性差异。
Objective To analysis the distribution and clinical characteristics of gene mutations in patients with glucose-6-phosphate dehydrogenase(G6 PD) deficiency in Sichuan, Yunnan and Guizhou, so as to provide laboratory evidence for clinical diagnosis and treatment of the disease. Methods G6 PD gene mutations were detected by multicolor probe fluorescent PCR melting curve method(MMCA) in 450 patients with suspected G6 PD deficiency(342 males and 108 females). The correlations between gene mutation types and clinical symptoms were analyzed. Results Among the 450 suspected patients, there were 215 cases(172 males and 43 females) of G6 PD single gene mutations, as 11 gene mutation types were found: 1388 G>A(29.78%), 1376 G>T(24.65%), 1024 C>T(22.33%), 95 A>G(12.09%), 871 G>A(4.05%), 392 G>T(2.33%), 517 T>C(1.39%), 487 G>T(0.93%), 1004 C>A(0.93%), 1387 C>T(0.47%), 1360(0.47%); and 1 female case contained 1388 G>A and 1004 C>A mutations. The dominant genotypes were 1388 G>A, 1376 G>T and 1024 C>T in Sichuan, Yunnan and Guizhou. The first two mutation sites of male and female children were both 1388 G>A(26.7%, 41.9%) and 1376 G>T(26.2%, 18.6%), and followed with 1024 C>T(25.0%) in male children, while 95 A>G(14.0%) in female. The main genotypes in children less than 1 year old were 1024 C>T(28.0%), 1388 G>A(25.6%) and 1376 G>T(25.0%), while they were 1388 G>A(43.1%), 1376 G>T(23.5%) and 95 A>G(15.7%) in those older than 1 year old. The enzymatic activity of the male children was significantly lower than that of the female children, but there was no statistical difference in genotype enzyme activity in the same sex(F=0.680 and 1.629, P=0.666 and 0.177). Anemia, jaundice, urine color change and hepatomegaly were the main clinical manifestations, and there was no significant difference in clinical manifestations among different genotypes(P>0.05). Conclusion The dominant gene mutations are 1388 G>A, 1376 G>T, and 1024 C>T in Han children with G6 PD deficiency in Sichuan, Yunnan and Guizhou in Southwest China. Gene mutation types are diversely distributed. Mutations may be correlated to gender and age at first onset, and there is no significant difference in clinical manifestation or enzyme activity among mutants.
Objective To analysis the distribution and clinical characteristics of gene mutations in patients with glucose-6-phosphate dehydrogenase(G6 PD) deficiency in Sichuan, Yunnan and Guizhou, so as to provide laboratory evidence for clinical diagnosis and treatment of the disease. Methods G6 PD gene mutations were detected by multicolor probe fluorescent PCR melting curve method(MMCA) in 450 patients with suspected G6 PD deficiency(342 males and 108 females). The correlations between gene mutation types and clinical symptoms were analyzed. Results Among the 450 suspected patients, there were 215 cases(172 males and 43 females) of G6 PD single gene mutations, as 11 gene mutation types were found: 1388 G>A(29.78%), 1376 G>T(24.65%), 1024 C>T(22.33%), 95 A>G(12.09%), 871 G>A(4.05%), 392 G>T(2.33%), 517 T>C(1.39%), 487 G>T(0.93%), 1004 C>A(0.93%), 1387 C>T(0.47%), 1360(0.47%); and 1 female case contained 1388 G>A and 1004 C>A mutations. The dominant genotypes were 1388 G>A, 1376 G>T and 1024 C>T in Sichuan, Yunnan and Guizhou. The first two mutation sites of male and female children were both 1388 G>A(26.7%, 41.9%) and 1376 G>T(26.2%, 18.6%), and followed with 1024 C>T(25.0%) in male children, while 95 A>G(14.0%) in female. The main genotypes in children less than 1 year old were 1024 C>T(28.0%), 1388 G>A(25.6%) and 1376 G>T(25.0%), while they were 1388 G>A(43.1%), 1376 G>T(23.5%) and 95 A>G(15.7%) in those older than 1 year old. The enzymatic activity of the male children was significantly lower than that of the female children, but there was no statistical difference in genotype enzyme activity in the same sex(F=0.680 and 1.629, P=0.666 and 0.177). Anemia, jaundice, urine color change and hepatomegaly were the main clinical manifestations, and there was no significant difference in clinical manifestations among different genotypes(P>0.05). Conclusion The dominant gene mutations are 1388 G>A, 1376 G>T, and 1024 C>T in Han children with G6 PD deficiency in Sichuan, Yunnan and Guizhou in Southwest China. Gene mutation types are diversely distributed. Mutations may be correlated to gender and age at first onset, and there is no significant difference in clinical manifestation or enzyme activity among mutants.
引文
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[17] 谭忠友,余超.261例G6PD缺乏症患儿基因突变型与血型关系的探讨[J].川北医学院学报,2017,32(5):712-714.
[18] 张格,于洁,李蕙,等.31例G6PD缺乏症患儿基因突变与临床表现分析[J].中国小儿血液与肿瘤杂志,2015,20(6):299-304.
[19] 刘维亮,李芳,何志旭,等.贵州省 17 例葡萄糖-6-磷酸脱氢酶缺乏症患者临床特征和致病基因突变分析[J].中华实用儿科临床杂志,2014,29(20):1564-1567.
[20] 黄盛文,吴娴,许吟,等.贵阳地区新生儿 G6PD 缺乏症分子筛查结果分析[J].重庆医学,2016,45(11):1505-1507.
[21] 杨昭庆,褚嘉佑,许绍斌,等.云南省葡萄糖-6-磷酸脱氢酶基因突变型的初步研究[J].中华血液学杂志,2000,21(10):509-511.
[22] 王琼,黎曼侬,黄烁丹,等.滤纸干血斑用于昆明地区人群葡萄糖-6-磷酸脱氢酶缺乏症基因突变的应用性研究[J].云南医药,2016,37(3):300-303.
[23] 陈运生,李长钢,陈小文,等.中国人两种常见G6PD基因突变型的酶活性研究[J].中国热带医学,2007,7(5):666-668.
[2] Yan JB,Xu HP,Xiong C.Rapid and reliable detection of glucose-6-phosphate dehydrogenase (G6PD) gene mutations in Han Chinese using high-resolution melting allalysis[J].J Mol Diagn,2010,12(3):305-311.
[3] 林芬,杨辉,杨立业.我国葡萄糖-6-磷酸脱氢酶缺乏症的分布特征和基因突变[J].分子诊断与治疗杂志,2016,8(2):73-77.
[4] 刘素云,易爱兰.儿童葡萄糖-6 磷酸脱氢酶缺乏症 C1159T 基因分析[J].临床儿科杂志,2016,34(2):158.
[5] 赵学峰,李毅坚,蔡甜,等.佛山地区孕产妇G6PD基因缺陷调查及干预模式研究[J].检验医学与临床,2016,13(9):1172-1176.
[6] 李文瑞,叶敏南,彭琪,等.东莞地区469例 G6PD 缺乏症基因突变类型分析[J].国际检验医学杂志,2014,35(17):2287-2288.
[7] 詹小芬,杨辉,杨惠钿,等.广东潮州地区新生儿葡萄糖-6-磷酸脱氢酶缺乏症基因突变分析[J].重庆医科大学学报,2014,39(12):1749-1752.
[8] 陈荣誉,陈少科,谢波波,等.广西部分地区496例G6PD基因检测结果分析[J].中国优生与遗传杂志,2014,22(11):20-22.
[9] 刘秀莲,王洁,黄慈丹,等.海口地区新生儿G6PD基因突变分析[J].分子诊断与治疗杂志,2017,9(3):165-167.
[10] 刘晗,蒋玮莹.人类葡萄糖-6-磷酸脱氢酶的分子生物学研究进展[J].国际遗传学杂志,2009,32(1):18-22.
[11] 王艳宁,赵敏芳,吴曙粤.新生儿黄疸与G6PD基因突变关系的研究进展[J].吉林医学,2015,36(1):105-107.
[12] 林彩娟,罗超,李旺,等.2014 年广西地区新生儿 G6PD 筛查及确诊情况分析[J].中国妇幼保健,2015,30(31):5361-5363.
[13] 林芬,吴教仁,杨辉,等.粤东潮州地区葡萄糖-6-磷酸脱氢酶缺乏症患者G6PD基因的突变类型[J].中华医学遗传学杂志,2016,33(1):26-29.
[14] 朱钰钰,林芬,吴教仁,等.潮州地区糖尿病与葡萄糖-6-磷酸脱氢酶缺乏症的相关性研究[J].中国实用医药,2017,12(23):8-10.
[15] 陈开科,符菊秀,熊先会,等.海南省澄迈县人群G6PD缺乏症基因突变分析[J].基础医学与临床,2016,36(9):1222-1226.
[16] 余超,于洁,宪莹,等.儿童G6PD缺乏症355例临床分析[J].中国小儿血液与肿瘤杂志,2015,20(3):126-130.
[17] 谭忠友,余超.261例G6PD缺乏症患儿基因突变型与血型关系的探讨[J].川北医学院学报,2017,32(5):712-714.
[18] 张格,于洁,李蕙,等.31例G6PD缺乏症患儿基因突变与临床表现分析[J].中国小儿血液与肿瘤杂志,2015,20(6):299-304.
[19] 刘维亮,李芳,何志旭,等.贵州省 17 例葡萄糖-6-磷酸脱氢酶缺乏症患者临床特征和致病基因突变分析[J].中华实用儿科临床杂志,2014,29(20):1564-1567.
[20] 黄盛文,吴娴,许吟,等.贵阳地区新生儿 G6PD 缺乏症分子筛查结果分析[J].重庆医学,2016,45(11):1505-1507.
[21] 杨昭庆,褚嘉佑,许绍斌,等.云南省葡萄糖-6-磷酸脱氢酶基因突变型的初步研究[J].中华血液学杂志,2000,21(10):509-511.
[22] 王琼,黎曼侬,黄烁丹,等.滤纸干血斑用于昆明地区人群葡萄糖-6-磷酸脱氢酶缺乏症基因突变的应用性研究[J].云南医药,2016,37(3):300-303.
[23] 陈运生,李长钢,陈小文,等.中国人两种常见G6PD基因突变型的酶活性研究[J].中国热带医学,2007,7(5):666-668.