我国Marfan综合征基因连锁标记的研究

为了探索对Ｍａｒｆａｎ综合征进行产前诊断和症状前诊断的方法，应用１５号染色体ＦＢＮ１基因内两个多态位点ＴａｑⅠ限制性片段长度多态性（ＲＦＬＰ）和（ＴＡＡＡＡ）ｎ扩增片段长度多态性（Ａｍｐ－ＦＬＰ）为遗传标记，在正常人群中检出前者有５．０ｋｂ（＋）和６．０ｋｂ（－）两种等位基因，基因频率各为２７％和７３％；后者有１５０ｎｔ（１）和１６０ｎｔ（２）两种等位基因，基因频率分别为３１％和６９％，未见白种人中的罕见变异型。两个患病家系的单倍型分离分析表明，致病基因均与－，２单倍型连锁，提示中国人群中Ｍａｒｆａｎ综合征也与ＦＢＮ１基因连锁。以该基因内的多态位点为遗传标记，可对该病的一些家系成员进行产前或症状前诊断。

LINKED MARKER ANALYSIS OF MARFAN SYNDROME IN CHINA

TaqI RFLP and (TAAAA)n Amp FLP polymorphic sites in the FBN1 gene on chromosome 15 were used as genetic markers. Analysis of random normal subjects showed two RFLP alleles, 5.0kb( ) and 6.0kb(-), with allele frequencies 27% and 73% respectively, and two Amp FLP alleles, 150nt(1) and 160nt(2), with allele frequencies 31% and 69% respectively. The rare variants of Amp FLP alleles in Caucasians were not noted in these Chinese subjects. Haplotype segregation analysis of two affected families indicated that the defective genes in both families were linked to -,2 haplotype. Our results imply that Marfan syndrome is also linked to FBN1 gene in Chinese population. Prenatal and presymptomatic diagnosis can be made in some family members by using these intragenic markers.