中国北方一马凡氏综合征家系致病基因突变研究

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

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。

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 muta- tion was identified using direct sequencing. Results A missense mutation g640a in exon6 of FBN1 gene was identi- fied in affected patients of this chinese family. The correspond animo acid change was gly241ser. Restrictive endonu- clease site Eag [ was eliminated. This mutation was not found in unaffected family members of this family. Conclu- sion A recurrent mutation g640a of FBN1 gene with glycine to serine change is responsible for the Marfan syn- drome patients in a chinese family.