马凡综合征一家系的临床研究及致病基因连锁分析

目的研究一个中国人马凡综合征(Marfan sydrome,MFS)家系的临床特点,并通过基因连锁分析的方法对该家系的致病基因进行定位研究。方法收集一个MFS家系,对家系所有成员进行全面详细的眼科及全身临床检查。确定其临床表型及遗传方式后,在位于MFS的已知基因FBN1、TGFBR1、TGFBR2附近选取微卫星标记物进行连锁分析。经ABI3130型遗传分析仪、Genscan2.1收集数据,Genotyper2.1进行基因分型,Link-age软件计算两点LOD值。结果该家系的遗传方式为常染色体显性遗传,家系中所有患者均具有典型的晶状体脱位、高度近视及MFS的特征性骨骼改变。仅有2例患者表现为心血管系统的异常。与该家系连锁的染色体微卫星标记物为D3S1609和D3S2432,其最大的LOD值为3.22。结论此家系为常染色体显性遗传型MFS,其致病基因位于3号染色体的D3S1609和D3S2432之间,位于该区间内的已知基因TGFBR2的突变可能是导致该家系致病的分子基础。

Clinical study and linkage analysis for a Chinese Marfan syndrome family

Objective To study the clinical phenotype in a Chinese family with Marfan syndrome(MFS) and determine the candidate gene using linkage analysis.Methods A detailed clinical ophthalmic and complete physical examinations were performed for all patients in the MFS family.The microsatellite markers which near known MFS candidate genes(FBN1,TGFBR1,TGFBR2) were used as genetic markers after determining the clinical phenotype and the mode of inheritance.Multiple amplitude of microsatellite sequence was performed using PCR.Two-point LOD scores were calculated using the Linkage program.Results The affected members in the pedigree had classical phenotype of MFS,they were inherited as an autosomal dominant trait.All patients in this family had various bilateral lens dislocation,high myopia and skeletal features.Only 2 patients had cardiovascular malformations.The disease phenotype co-segregated with the markers D3S1609 and D3S2432 which were near from TGFBR2 gene,the maximum LOD score was 3.22.Conclusion This family has autosomal dominant trait,the candidate gene locate in D3S1609 and D3S2432 near from TGFBR2 gene,the known TGFBR2 gene mutation may be the molecular basis for MFS.