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 found to cause Marfan syndrome, a dominantly inherited disorder characterised by clinically variable skeletal, ocular, and cardiovascular abnormalities. In this study we screened all 65 exons of the fibrillin-1 gene in 20 Marfan syndrome families where at least two affected individuals were characterised and available for analysis, another 30 families with only one affected member available for analysis, and in 10 sporadic cases. In large well-characterised families with more than four affected 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 mutation detection rate was 17% (5/30), and in sporadic cases it was 20% (2/10). In addition, we found eight neutral polymorphisms. Twelve of the 17 disease-causing mutations identified have not been previously described, thus raising the total number of different fibrillin-1 mutations reported to 85 in 94 unrelated cases.