Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides

Kainulainen, K.; Sakai, L.Y.; Child, A.; Pope, F.M.; Puhakka, L.; Ryhänen, L.; Palotie, A.; Kaitila, I.; Peltonen, L.

Proceedings of the National Academy of Sciences of the United States of America 89(13): 5917-5921


ISSN/ISBN: 0027-8424
PMID: 1631074
DOI: 10.1073/pnas.89.13.5917
Accession: 007974243

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Biochemical and molecular genetic studies have recently suggested that mutations in the gene coding for fibrillin on chromosome 15 result in Marfan syndrome. To our knowledge, only one mutation in the fibrillin gene has been published. Here we report the results of screening 20 unrelated MFS patients for mutations in fibrillin cDNA by the single-strand conformation polymorphism technique. We found two mutations, both of which appear in the heterozygote form and code for a shortened fibrillin polypeptide. The first mutation is a large in-frame deletion of 366 bases of the fibrillin mRNA, shown to result in a truncated but secreted polypeptide found in the fibroblast culture of the patient. The second mutation is a G-to-A transition resulting in the substitution of a stop codon for a tryptophan codon and thus predicting the premature termination of the polypeptide chain. We screened 60 other, unrelated MFS patients for these mutations as well as for the previously reported mutation (arginine-239 to proline) and found none of the three mutations in any of these patients. These data suggest that most MFS families carry their own distinct mutation.