Alternative splicing of exon 37 of FBN1 deletes part of an 'eight-cysteine' domain resulting in the Marfan syndrome

A child and his father had the skeletal and cardiovascular manifestations of Marfan syndrome due to a heterozygous G(+5) --> T transversion in intron 37 of the FBN1 gene. Cultured dermal fibroblasts preferentially used an alternative splice site in exon 37 that resulted in the loss of the 3' 48 nucleotides of this exon. The translational reading frame was maintained with deletion of lysine 1568 to threonine 1582 and splitting of the codons for glycine 1567 and serine 1583 to yield GCC for alanine. The deletion removed two cysteine residues as well as a potential N-linked oligosaccharide attachment site from the '8-cysteine' domain encoded by exons 37 and 38.