中国北方一马凡氏综合征家系致病基因突变研究

目的研究确定我国北方一马凡氏综合征(MFS)家系致病基因突变位点。方法对马凡氏综合征一家系进行临床研究和系谱分析。采集家系中3例患者和3例健康成员的静脉血,提取基因组DNA。应用聚合酶链反应(PCR)扩增马凡氏综合征致病基因原纤维蛋白1(FBN1)基因外显子及外显子-内含子接头处,直接测序确定致病的基因突变。结果马凡氏综合征患者的FBN1基因外显子6发生了错义突变,cDNA 640位的鸟嘌呤被腺嘌呤取代(G640A);对应的甘氨酸改变为丝氨酸。突变后EagⅠ内切酶位点消失。该突变在家系中表现为与疾病共分离。结论 FBN1基因突变G640A是该马凡氏综合征家系的致病基因突变。

Identify the mutation gene of a family with Marfan syndrome in north china

Objective To identify the mutation gene of a family with Marfan syndrome in north china.Methods Clinical observation and pedigree analysis were undertaken in a family with Marfan syndrome.Venous blood was drawn from 3 affected and 3 unaffected subjects.Genomic DNA was extracted.Mutation of FBN1 gene which has been found to cause Marfan syndrome was screened by PCR of the exons and exons-intron boundaries.The mutation was identified using direct sequencing.Results A missense mutation g640a in exon6 of FBN1 gene was identified in affected patients of this chinese family.The correspond animo acid change was gly241ser.Restrictive endonuclease site EagⅠwas eliminated.This mutation was not found in unaffected family members of this family.Conclusion A recurrent mutation g640a of FBN1 gene with glycine to serine change is responsible for the Marfan syndrome patients in a chinese family.