29例汉族马凡综合征患者的FBN1基因突变分析

Analysis of FBN1 mutations in 29 patients with Marfan syndrome among Han population

目的对29例汉族马凡综合征(Marfan syndrome,MFS)患者的原纤蛋白-1(fibrillin-1,FBN1)基因进行突变筛查,探讨MFS与FBN1基因突变的关系。方法提取29例患者外周血全基因组DNA,应用PCR技术对FBN1的65个外显子进行扩增,应用变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)对患者FBN1的65个外显子进行突变筛查,对DHPLC检测出图形异常的PCR扩增片段用DNA测序鉴定突变位点和类型。结果在12例MFS患者中发现12种FBN1突变。其中有8种为新的突变,分别为2359A>T(S787C)、3380G>T(G1127V)、4151T>C(M1384T)、4244G>A(C1415Y)、6071G>T(C2024F)、IVS2+1G>T、IVS37+5G>A和7970C>G+7971delC。另外4种为已报道突变,包括3037G>A(G1013R)、6049T>C(C2017R)、4429G>T(E1477X)和4930C>T(R1644X)。结论 FBN1基因突变可能是12例MFS患者的致病因素。

Objective To detect FBN1 mutation by screening the gene form 29 patients with Marfan syndrome（MFS ） among Han population and to investigate the correlation between FBN1 gene mutation and MFS. Methods Genomic DNAs were extracted from whole blood sample of 29 patients. All 65 exons of FBNI were amplified by polymerase chain reaction（PCR） respectively. Mutations were screened by denaturing high performance liquid chromatography（DHPLC）, followed by DNA sequencing of the PCR products which had different DHPLC profiles from the norm and to identify the position and type of mutations. Results A total of 12 FBN1 mutations in 12 MFS patients were identified, of which 8 were novel, comprised of 2359A〉T（S787C）, 3380G〉T（GI127V）, 4151T〉C（M1384T）, 4244G〉A（C1415Y）, 6071G〉T（C2024F）, IVS2＋IG〉T, IVS37＋5G〉A and 7970C〉G＋7971 delC. The other 4 mutations have been reported, including 3037G〉A（G1013R）, 61N9T〉C （C2017R）, 4429G〉T（E1477X） and 4930C〉T（R1644X）. Conclusion FBN1 gene mutation may be the pathogenic factors of the 12 MFS patients.