16例经典型Fabry病患者的临床表现和基因突变分析  

Clinical manifestations and mutation study in 16 Chinese patients with Fabry disease

作　　者：孟岩[1] 张为民[2] 施惠平[1] 魏珉[3] 黄尚志[1] 

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院基础学院医学遗传学系WHO遗传病社区控制合作中心,100005 [2]中国医学科学院北京协和医院中心实验室 [3]中国医学科学院北京协和医院儿科

出　　处：《中华医学杂志》2010年第8期551-554,共4页National Medical Journal of China

基　　金：科技部“十一五”国家科技支撑计划（2006BIA05A08）项目;北京市科学技术委员会研发攻关类基金（D0906005040491） 志谢 北京协和医院眼科秦梅教授对部分患者进行眼科检查及患者和家属的配合

摘　　要：目的了解中国人经典型Fabry病患者的临床特征，并进行致病基因突变分析以提高国内对Fabry病的诊断水平。方法对16例无血缘关系、经外周血白细胞α-半乳糖苷酶A活性检测确诊的Fabry病男性患者的临床表现进行总结分析；提取患者外周血DNA，对α-半乳糖苷酶A基因（GLA基因）的每个外显子及旁侧内含子序列进行PCR产物直接测序；对所发现的新突变进行保守性分析及群体筛查以确定其致病性。结果16例患者年龄为11—40岁，均具有Fabry病的典型特征，从发病到确诊拖延4～30年。在16例先证者中检测到14个突变，其中错义突变11个、无义突变1个、单碱基缺失1个、剪接位点突变1个，其中8个为新突变（c．119C〉A、c．275A〉T、c．520T〉C、c．547G〉C、c．647A〉G、c.929T〉G、c．1045T〉A、IVS1—1G〉A）。群体酶切筛查均未发现有与患者相同的突变。新的错义突变在不同物种GLA基因中均具高度保守性。结论Fabry病在国内的误诊率高；中国人GLA基因突变无突变热点；基因突变检测是诊断Fabry病的可靠方法。Objective To investigate the clinical manifestations and to characterize mutations of the GLA gene in Chinese patients with Fabry disease so to enhance the diagnosis of Fabry disease. Methods Sixteen Chinese affected males （from 16 unrelated families） with the classic phenotype of Fabry disease were investigated. The patients were diagnosed by a deficiency of α-galactosidase A （α-Gal A） activity. All seven exons and the neighboring intronic sequences of GLA gene were analyzed by PCR amplification and automated sequencing. Results A total of 14 mutations were identified including 12 single-base substitutions（ 11 missense and 1 nonsense mutations） , 1 small deletion and 1 splicing mutation. Eight novel mutations（ c. 119 C 〉 A, c. 275 A 〉 T, c. 520T 〉 C, c. 547G 〉 C, c. 647A 〉 G, c. 929T 〉 G, c. 1045T 〉 A, IVS1-IG 〉 A）were identified. The novel mutations were not tested by RFLP on 100 GLA alleles in Chinese population, and were highly conservative in mammalian species. Conclusion Fabry disease is often misdiagnosed in China. There is no hot spot for mutations in Chinese patients. GLA gene mutation analysis is a reliable method to diagnosis for Fabry disease.

关 键 词：法布里病α半乳糖苷酶 突变 GLA基因 

分 类 号：R596[医药卫生—内科学]