FBN1 Genetic Diagnosis By Haplotype Analysis In Chinese Patients With Marfan Syndrome

Objective:To establish a haplotype segregation method using the microsatellite polymorphism in families with Marfan's syndrome (MFS) for early diagnosis, management, and genetic counseling. To evaluate microsatellite detection in presymptomatic diagnosis of Marfan's syndrome. Methods :Genomic DNA was extracted from peripheral blood in 4 families with Marfan' syndrome and 40 unrelated and unaffected control subjects. The four microsatellites in the flanking of the FBNI gene on chromosome 15 were used as inheritance markers. DNA fragments were amplified by polymerase chain reaction (PCR). Subsequently, the PCR products were analyzed by capillary electrophoresis with fluorescence detection. The haplotype-segregation analysis was performed in the 4 kindreds with Marfan's syndrome and the 40 unrelated and unaffected control subjects. Results:The results of haplotype analysis for the 40 unrelated and unaffected control subjects were different from those reported previously. The mutant alleles in the 4 kindreds with Marfan'ssyndrome were cosegerated with the 8/7/3/15,7/6/3/14, 7/7/3/10 and 13/7/3/10 respectively. The results of haplotype-segregation analysis accorded with the phenotypes of the tested patients with Marfan's syndrome. The established method of PCR-capillary electrophoresis showed to be highly sensitive and reproducible for the four FBNl microsatellite markers detection. Conclusion:( 1) The method of PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection can be used as a molecular diagnosis method for Marfan's syndrome.(2) It is suggested that the frequencies of haplotype for the four FBNl microsatellites in Chinese are different from those reported previously.(3) Our results of haplotype-segregation analysis indicate that the mutant allele is linked to FBNl gene in the 4 kindreds with Marfan's syndrome in Fujian Province. Our method can be used in presymptomatic diagnosis of Marfan's syndrome...