Smith-Fineman-Myers综合征的精细定位及候选基因分析  

Fine mapping of Smith-Fineman-Myers syndrome and exclusion of GPC3,GPCR2,MST4 and GLUD2 as candidate genes

作　　者：刘奇迹[1] 龚瑶琴[1] 李江夏[1] 张锡宇[1] 高贵敏[1] 郭亦寿[1] 

机构地区：[1]山东大学医学院医学遗传学研究所,济南250012

出　　处：《中华医学遗传学杂志》2004年第3期198-202,共5页Chinese Journal of Medical Genetics

基　　金：国家"973"项目 (2 0 0 1 CB51 0 30 3);国家杰出青年基金(30 2 2 50 2 0 )~~

摘　　要：目的　精细定位 Smith- Fineman- Myers综合征 ( Smith- Fineman- Myers syndrome,SFMS)致病基因 ,缩小致病基因候选区域。方法　从原定位区域中选择了 13个新的多态位点 ,采用聚合酶链反应( polymerase chain reaction,PCR)结合变性聚丙烯酰胺凝胶电泳方法 ,分析 SFMS家系中各成员多态位点基因型。从缩小的区域中根据已知基因的功能 ,从中选择了 GPC3、GPCR2、MST4和 GL UD2作为候选基因 ,设计了扩增全部外显子和内含子外显子接头序列的引物 ,通过直接测序法对家系中的患者进行了突变检测。结果　连锁分析结果将 SFMS定位区域缩小到 10 .18Mb,所有 4个候选基因在患者中未检测到突变。结论　候选区域的缩小 ,为最终分离 SFMS的致病基因奠定了基础 ,GPC3、GPCR2、MST4和 GL UD2不是中国山东地区Objective Smith-Fineman-Myers syndrome (SFMS) is an X-linked mental retardation syndrome. The authors had ascertained a large Chinese family with SFMS from Shandong and had mapped the disease locus to an interval of 19.8Mb on Xq25 flanked by markers DXS8064 and DXS8050. Further investigation suggested that SFMS exhibited locus heterogeneity. In this study for facilitating the identification of the gene responsible for SFMS, the additional markers were analyzed to narrow down the candidate region, and four candidate genes (GPC3, MST4,GPCR2 and GLUD2) were chosen and screened for disease-causing mutation. Methods PCR and denaturing polyacrylamide gel electrophoresis were used to genotype 13 new polymorphic markers distributed within the candidate region. Mutation detection was accomplished by sequencing the exons and intron-exon junctions of the candidate genes. Results By analyzing 13 additional polymorphic markers, SFMS candidate region can be reduced to an interval of 10 18 Mb bounded by XSTR3 and XSTR4, and no disease-causing mutation was identified in the coding regions of four candidate genes. Conclusion GPCR2,GPC3, MST4 and GLUD2 were excluded as pathogenic genes for SFMS. The refined SFMS locus will assist in the identification and characterization of other candidate genes for SFMS.

关 键 词：Smith—Fineman—Myers综合征 连锁分析 基因定位 突变分析 

分 类 号：R596.1[医药卫生—内科学]