Novel exon skipping mutation in the fibrillin-1 gene: Two 'hot spots' for the neonatal Marfan syndrome

The Marfan syndrome is an autosomal dominant heritable disorder of connecti ve tissue that involves principally the skeletal, ocular, and cardiovascula r systems. The most severe end of the phenotypic spectrum, the neonatal Mar fan syndrome (nMFS), is characterized by pronounced atrioventricular valve dysfunction, and death often occurs within the first year of life due to co ngestive heart failure. Mutations in the gene coding for fibrillin-1, FBN1, are known to cause Marfan syndrome, and have been identified in almost all exons of FBN1. Here, we describe a novel mutation affecting the invariant + 1 position of the splice donor site in intron 31, associated with skippin g of exon 31, in a patient with nMFS. Published reports of nMFS are reviewe d and a strict definition for nMFS is suggested. If this definition is used , all nMFS mutations reported to dale lie in one of two hot spots, comprisi ng mainly missense mutations in FBN1 exons 24-27 and mutations causing skip ping of exon 31 or 32.