11例中国人粘多糖贮积症Ⅰ型轻型患者的基因突变检测  

Mutation analysis of 11 Chinese patients with attenuated mucopolysaccharidosis type Ⅰ

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

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,北京100780 [2]中国医学科学院基础医学研究所遗传学系,北京100730 [3]中国医学科学院中心实验室,北京100730

出　　处：《中华医学遗传学杂志》2011年第2期147-151,共5页Chinese Journal of Medical Genetics

基　　金：国家重点基础研究发展计划（973计划,2005CB522507）;＂十一五＂国家科技支持计划项目（2006BAI05A07）

摘　　要：目的 对经酶学确诊的粘多糖贮积症Ⅰ型患者进行α-L-艾杜糖苷酸酶（α-L-iduronidase,IDUA）基因突变检测,了解中国北方地区粘多糖贮积症Ⅰ型轻型患者基因突变特点.方法 应用PCR扩增技术及直接测序技术对11例中国北方地区经酶学确诊的粘多糖贮积症Ⅰ型患者IDUA基因14个外显子及相邻区域进行突变筛查,同时进行亲本来源分析.结果 11例患者中检测出7种基因突变：A79V、R89Q、R89w、E178K、G197S、L346R和W626X.7种突变均为已报道过子,11例中6例患者为纯合改变,1例为无义突变杂合子;发现了9种已知多态性位点.结论 中国北方地区粘多糖贮积症Ⅰ型轻型患者IDUA基因的突变特点可能不同于其他国家和地区.Objective Mucopolysaccharidosis type Ⅰ （MPS Ⅰ ） is an autosomal recessive diseaseresulting from the deficiency in the lysosomal enzyme α-L-iduronidase （IDUA）. The present study was conducted to identify IDUA gene mutations in attenuated （MPS Ⅰ H/S and MPS Ⅰ S） patients with MPS Ⅰin northern China. Methods Fourteen exons with adjacent intronic sequences of the IDUA gene in 11 MPS Ⅰ patients were amplified by polymerase chain reaction （PCR）, and the PCR products were sequenced directly and origin analysis was conducted. Results Seven mutations were detected in the 11 MPS Ⅰ patients, i.e., c. 236 C〉T（p. A79V）, c. 266 G〉A（p. R89Q）, c. 265 C〉T（p. R89W）, c. 532G〉A（p.E178K）, c. 589G〉A（p. G197S）, c. 1037T〉G（p. L346R）, and c. 1877 G〉A（p. W626X）. All of them were known mutations. Six patients were homozygotes and 1 was heterozygote with nonsense mutation. In addition, 9 reported single nucleotide polymorphism （SNP） were detected, i. e., p. A8, p. A20, p. H33Q,p. R105Q, p. A314, p. A361T, p. T388, p. T410 and p. V454I. Conclusion The mutation spectrum of the IDUA gene in attenuated MPS Ⅰ Chinese patients may be different from that in patients from other countries.

关 键 词：粘多糖贮积症Ⅰ型 基因突变 α-L-艾杜糖苷酸酶基因 

分 类 号：R725.8[医药卫生—儿科]