四例马凡综合征患者的FBN1基因突变分析及产前诊断  

Mutation analysis and prenatal diagnosis of FBN1 gene mutations for four patients with Marfan syndrome

作　　者：宋士秋[1] 赵保健 李爽 张建群[1] 王慧 贾婵维 张凤环 张旭 谢进生[1] 

机构地区：[1]首都医科大学附属北京安贞医院心外科,北京100029 [2]北京德博全基因检测技术研究所 [3]安贞医院妇产科 [4]北京妇产医院生殖医学中心

出　　处：《中华医学遗传学杂志》2013年第5期534-538,共5页Chinese Journal of Medical Genetics

摘　　要：目的对4例马凡综合征（Marfan syndrome，MFs）患者进行原纤维蛋白一1基因（fibrillin-1，FBNl）突变检测及产前诊断，为患者提供病因诊断和遗传咨询。方法应用PCR扩增和DNA测序对4例典型的MFS患者进行FBNl基因筛查。确定突变类型后，于孕18～20周穿刺抽取羊水，抽提DNA，PCR扩增FNBl基因，对PCR产物进行双向测序。结果例1FBNl基因第46内含子的＋1位碱基发生置换（IVS46＋1G〉A）；例2第35外显子的4453位碱基发生错义突变c．4453T〉G（Cysl485Gly）；例3第21外显子2585位碱基发生错义突变e．2585G〉A（Cys862Tyr）；例4第28外显子3536位碱基A缺失e．3536delA。C．4453T〉G（Cysl485Gly）、C．2585G〉A（Cys862Tyr）和C．3536delA为新突变。4例胎儿羊水的标本也分别检测到IVS46＋1G〉A、C．4453T〉G（Cysl485Gly）、C．2585G〉A（Cys862Tyr）和C．3536delA突变。结论FBNl基因筛查可以检测出患者及其家系中胎儿的突变位点和类型，具有明确的诊断价值，有助于遗传咨询。Objective To screen for mutations of fibrillin-1 （FBN1）gene in 4 patients with Marfan syndrome in order to provide prenatal diagnosis and genetic counseling. Methods Potential mutations of the FI3N1 gene in the probands were detected with PCR and DNA sequencing. Subsequently, genomic DNA was extracted from amniotie fluid obtained between 18 to 20 weeks gestation. The mutations were confirmed with denaturing high-performance liquid chromatography- robust microsatellite instability （DHPLC-MSI） analysis with maternal DNA as reference. The products were further analyzed by direct sequencing and BLAST search of NCBI database. Results An IVS46 4- 1G〉A substitution was identified in patient A at ＋1 position of intron 46 of the FBN1 gene. Two novel missense mutations （c. 4453T〉G, Cys1485Gly） were respectively discovered at positions 4-4453 of intron 35 in patient B and position 4-2585 of intron 21 in patient C. In patient D, a novel deletion （c. 3536 delA） was found at position 4-3536 of intron 28. In all of the 4 cases, the same mutations have been identified in the fetuses. Conclusion FBN1 gene analysis can provide accurate diagnosis of Marfan syndrome for both probands and fetuses, which will facilitate both prenatal diagnosis and genetic counseling.

关 键 词：马凡综合征 变性高效液相色谱技术 原纤维蛋白-1 基因突变 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学]