한국인 Marfan 증후군의 유전자 변이 분석

Abstract

Background and Objectives：Marfan syndrome is an autosomal dominant heritable disease of connective tissue which is characterized by cardinal features mainly in the cardiovascular, ocular and skeletal systems. Aneurysms or dissections of the aorta are the major cardiovascular complications of the disorder causing early mortality. Mutations in the fibrillin-1 (FBN1) gene on chromosome 15q21.1 have been found to be major causes of Marfan syndrome. The purpose of this study was to characterize the molecular defect in Korean Marfan patients, thus contributing to the effort of correlating the genotype with the phenotype.

Subjects and Methods：We screened all 65 exons of the FBN1 gene in 14 subjects diagnosed as Marfan syndrome by the method of single strand conformation polymorphism-heteroduplex analysis.

Results：We found mutations in only 10 among 14 patients. This study identified 8 novel mutations and 2 previously reported mutations in 14 Korean Marfan patients. Two cases were nonsense mutations and 8 were missense mutations, including 3 frameshift. Seven cases of the mutations occurred in one of the 43 calcium binding epidermal growth factor-like domains within an FBN1 gene. Mutations in Marfan patients occurred variably over the whole field of this FBN1 gene.

Conclusion：Our results will contribute to the establishment of a database of Korean Marfan patients. Extending this study and using the database will help early detection of the disease and prevention of complications.