MUTATION SCREENING OF ALL 65 EXONS OF THE FIBRILLIN-1 GENE IN 60 PATIENTS WITH MARFAN-SYNDROME - REPORT OF 12 NOVEL MUTATIONS

Mutations in the fibrillin-1 gene on chromosome 15q21.1 have been foun d to cause Marfan syndrome, a dominantly inherited disorder characteri sed by clinically variable skeletal, ocular, and cardiovascular abnorm alities. In this study we screened all 65 exons of the fibrillin-1 gen e in 20 Marfan syndrome families where at least two affected individua ls were characterised and available for analysis, another 30 families with only one affected member available for analysis, and in 10 sporad ic cases. In large well-characterised families with more than four aff ected individuals, the detection rate for mutations rose to 78% (7/9), in families with either two or three affected members 27% (3/11). In families where only one affected family member was available, the muta tion detection rate was 17% (5/30), and in sporadic cases it was 20% ( 2/10). In addition, we found eight neutral polymorphisms. Twelve of th e 17 disease-causing mutations identified have not been previously des cribed, thus raising the total number of different fibrillin-1 mutatio ns reported to 85 in 94 unrelated cases. (C) 1997 Wiley-Liss, Inc.