MOLECULAR DIAGNOSTICS IN

MARFAN SYNDROME


The Marfan Syndrome (MFS1) is one of the most common inherited connective tissue disorders. It is inherited as an autosomal dominant and has a prevalence of about 1/10,000. It has been estimated that about 15 - 30% of sporadic MFS1 cases are due to new mutations. It is now considered that virtually all cases of MFS1 are due to mutations in the fibrillin (FBN1) gene.

Mutation surveys of the FBN1 gene in affected individuals have demonstrated that nearly all families represent distinct FBN1 mutations. As a consequence, it is most effective to provide linkage analysis for families seeking genetic testing.


As depicted in the figure below, the FBN1 locus has yielded several polymorphic flanking and intragenic markers for linkage studies.




In nearly all cases with suitable family structure, accurate (> 99%) diagnostic predictions on MFS1 status can be made. As illustrated below, segregation of the "at risk" paternal P2 haplotype was detected in the fetus. This test was informative at both flanking and an internal FBN1 marker thus providing > 99% accuracy in the prediction of MFS1 status.