FBN1 exon 2 splicing error in a patient with Marfan syndrome

Mutations in FBN1 cause the autosomal dominant condition, Marfan syndrome. A single-base mutation that results in a skipping of exon 2 of FBN1 was fou nd in a Marfan patient. By sequencing this proband's entire FBN1 gene and c omparing the mutated DNA sequence with proband's unaffected family numbers, we confirmed this alteration was the causative mutation. The skipping of e xon 2 creates a frameshift and premature termination codon, and forms a tru ncated fibrillin-1 composed only of 55 amino acids of N-terminus plus 45 no nsense amino acids. The mRNA transcription levels of the mutated FBN1 allel e and the deposition of fibrillin-1 into extracellular matrix in fibroblast cells culture were assessed. (C) 2001 Wiley-Liss, Inc.