Novel approach to the molecular diagnosis of Marfan syndrome: Application to sporadic cases and in prenatal diagnosis

Iva Toudjarska, Michael W. Kilpatrick, Peter Lembessis, Scott Carra, Gary L. Harton, Michael E. Sisson, Susan H. Black, Harvey J. Stern, Zully Gelman-Kohan, Mordechai Shohat, Petros Tsipouras*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Marfan syndrome is an autosomal dominant disorder affecting the skeletal, ocular, and cardiovascular systems. Defects in the gene that encodes fibrillin-1 (FBN1), the main structural component of the elastin-associated microfibrils, are responsible for the disorder. Molecular diagnosis in families with Marfan syndrome can be undertaken by using intragenic FBN1 gene markers to identify and track the disease allele. However, in sporadic cases, which constitute up to 30% of the total, DNA-based diagnosis cannot be performed using linked markers but rather requires the identification of the specific FBN1 gene mutation. Due to the size and complexity of the FBN1 gene, identification of a causative Marfan syndrome mutation is not a trivial undertaking. Herein, we describe a comprehensive approach to the molecular diagnosis of Marfan syndrome that relies on the direct analysis of the FBN1 gene at the cDNA level and detects both coding sequence mutations and those leading to exon-skipping, which are often missed by analysis at the genomic DNA level. The ability to consistently determine the specific FBN1 gene mutation responsible for a particular case of Marfan syndrome allows both prenatal and pre-implantation diagnosis, even in sporadic instances of the disease.

Original languageEnglish
Pages (from-to)294-302
Number of pages9
JournalAmerican Journal of Medical Genetics
Issue number4
StatePublished - 1 Apr 2001


  • FBN1
  • Fibrillin-1
  • Marfan syndrome
  • Pre-implantation diagnosis
  • Prenatal diagnosis


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