黏多糖贮积症Ⅰ型二例基因突变检测及产前诊断  

Mutation analysis and prenatal diagnosis of 2 cases with mucopolysaccharidosis type Ⅰ

作　　者：王新宁[1] 魏珉[1] 施惠平[3] 邱正庆[1] 姚凤霞[2] 孟岩[3] 张为民[2] 

机构地区：[1]中国医学科学院 北京协和医学院 北京协和医院儿科,100730 [2]中国医学科学院 北京协和医学院 北京协和医院儿科 中心实验室,100730 [3]中国医学科学院基础医学研究所 北京协和医学院基础医学院医学遗传学系

出　　处：《中华儿科杂志》2011年第4期306-310,共5页Chinese Journal of Pediatrics

基　　金：国家重点基础研究发展计划（973计划）（2005CB522507）;“十一五”国家科技支撑计划项目（2006BAI05A07）

摘　　要：目的对黏多糖贮积症Ⅰ型病例进行基因检测，对再孕母亲进行产前诊断。方法用酶学检测方法确诊2例黏多糖贮积症Ⅰ型先证者；采用PCR扩增技术结合序列分析的方法，检测2例先证者血液及其再孕母亲羊水细胞中IDUA基因外显子及其两侧内含子。结果在2例经酶学检测确诊的先证者中共检测出4种基因突变：P．L238R、c．883InsC、c．531InsT、P．L346R，2种为插入突变，2种为错义突变。在先证者1母亲羊水细胞IDUA基因中未发现致病基因突变，羊水细胞中[DUA酶活性为9．0nmol/（h·mg蛋白）；在先证者2母亲羊水细胞IDUA基因中检测到与先证者相同的两个致病突变，羊水细胞中IDUA酶活性为0．5nmol／（h·mg蛋白）。结论从黏多糖贮积症Ⅰ型先证者发现的4种突变中，P．L346R为已知突变，P．L238R，e．883Insc，c．531InsT为首次发现的新突变。胎儿1未获得与先证者相同致病基因，为正常胎儿。胎儿2获得与先证者相同致病基因，为受累胎儿。产前基因诊断结果与酶学产前诊断结果相符合。Objective Mueopolysaccharidosis type I （ MPS I ; MIM# 252800） is an autosomal recessive disease that results from the deficiency in the lysosomal enzyme a-L-iduronidase（ IDUA）. IDUA is one of the enzymes involved in degradation of glycosaminoglycans heparan sulphate and dermatan sulphate. The deficiency of IDUA leads to widespread accumulation of partially degraded mueopo]ysaccharides inside lysosomes, resulting in progressive cellular and multiorgan dysfunction. Up to now there is no definitely effective treatment for this disorder, therefore it is important to provide an accurate genetic diagnosis and prenatal diagnosis for the MPS I families. This study was conducted to detect IDUA gene mutation in patients with MPS I and make a definite diagnosis of homozygote or heterozygote and make first trimester prenatal diagnosis. Method The 2 male probands included in this study were diagnosed as MPS I patients in Peking Union Medical College Hospital, case 1 was 2 years old and case 2 was 5 years old. Genomie DNA was extracted from leucocytes in the 2 patients and 2 mothers＇ cultured amniocytes. IDUA gene DNA sequence was amplified by polymerase chain reaction （PCR） and the PCR products were sequenced directly. Novel mutations were analyzed in 100 normal chromosomes. Result The genotype of case 1 was p. L238R/ c. 883InsC, while of case 2 was e. 531InsT/p. L346R. The fetal ease 1 did not inherit the same pathogenic mutations as proband 1, the activity of the IDUA in amnioeytes was 9.0 nmol/（ h·mg pr）. The fetal case 2 inherited the same pathogenic mutations with the proband, the genotype of fetal 2 was c. 531 InsT/p. L346R, the activity of the IDUA in amniocytes was 0.5 nmol/（ h·mg pr）. Conclusion Of the 4 mutations found in 2 MPS I patients, p. L238R, e. 883InsC, c. 531InsT were novel. The fetal case 1 was diagnosed as normal fetus while the fetus 2 was diagnosed as affected. The results of the two kinds of prenatal diagnosticmethods were correspondent with each other.

关 键 词：黏多糖贮积症Ⅰ型 产前诊断 基因 突变 IDUA基因 

分 类 号：R714.5[医药卫生—妇产科学]