PRENATAL-DIAGNOSIS AND A DONOR SPLICE-SITE MUTATION IN FIBRILLIN IN AFAMILY WITH MARFAN-SYNDROME

The Marfan syndrome, an autosomal dominant connective tissue disorder, is manifested by abnormalities in the cardiovascular, skeletal, and o cular systems. Recently, fibrillin, an elastin-associated microfibrill ar glycoprotein, has been linked to the Marfan syndrome, and fibrillin mutations in affected individuals have been documented. In this study , genetic linkage analysis with fibrillin specific markers was used to establish the prenatal diagnosis in an 11-wk-gestation fetus in a fou r-generation Marfan kindred. At birth, skeletal changes suggestive of the Marfan syndrome were observed. Reverse transcription-PCR amplifica tion of the fibrillin gene mRNA detected a deletion of 123 bp in one a llele in affected relatives. This deletion corresponds to an exon enco ding an epidermal growth factor-like motif. Examination of genomic DNA showed a G-->C transversion at the +1 consensus donor splice site.