DOUBLE MUTANT FIBRILLIN-1 (FBN1) ALLELE IN A PATIENT WITH NEONATAL MARFAN-SYNDROME

It is now well established that defects in fibrillin-1 (FBN1) cause th e variable and pleiotropic features of Marfan syndrome (MFS) and, at t he most severe end of its clinical spectrum, neonatal Marfan syndrome (nMFS). Patients with nMFS have mitral and tricuspid valve involvement and aortic root dilatation, and die of congestive heart failure, ofte n in the first year of life. Although mutations in classical MFS have been observed along the entire length of the FBN1 mRNA, mutations in n MFS appear to cluster in a relatively small region of FBN1, approximat ely between exons 24 and 34. Here we describe the appearance of two FB N1 mutations in a single allele of an infant with nMFS. The changes we re within six bases of each other in exon 26. One was a T3212G transve rsion resulting in an I1071S amino acid substitution and the second wa s an A3219T transversion resulting in an E1073D amino acid substitutio n, This is the first reported double mutant allele in FBN1.