Intrafamilial phenotype variation in Marfan syndrome ascertained by intragenic linkage analysis.
Marfan syndrome is an autosomal dominant fibrillinopathy caused by mutations of the fibrillin-1 (FBN1) gene. Although linkage analysis is often required to ascertain the disease status in family members, recombination is a problem. We analyzed 6 families including 18 patients using 4 intragenic microsatellite markers, located in intron 1, 5, 28, and 43, respectively, of the FBN1 gene. Haplotypes in all family members could be established, and segregation analysis showed no recombination between the markers and the disease. After confirming the diagnosis, intrafamilial analysis revealed clinical manifestations involving the ocular, cardiac, and skeletal systems. Intragenic linkage analysis in Marfan syndrome is very helpful in its diagnosis and management within affected families.
Lee
Ni-Chung
NC
Department of Pediatrics, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan.
Hwang
Betau
B
Chen
Chia-Hsiang
CH
Niu
Dau-Ming
DM
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D013624:Taiwan