Novel de novo nonsense mutation of FBN1 gene in a patient with Marfan syndrome

Abstract

Marfan syndrome is an autosomal-dominant disorder of the connective tissue that primarily involves the cardiovascular, ocular and skeletal systems (Judge and Dietz 2005). Mutations in FBN1 gene (which encodes a connective protein, fibrillin-1) are reported to be causal for this disease. Diagnosis is made on the basis of a set of clinical and genetic criteria that are termed the Ghent nosology (De Paepe et al. 1996). In the Ghent nosology, clinical features are assessed within seven body ‘systems’, to determine whether that system provides a major criterion, or only system involvement. Diagnosis of Marfan syndrome requires a major criterion in two systems and involvement of a third. To date, most of the reported mutations are missense mutations affecting the conserved cysteine residues or residues of the consensus sequence of calcium-binding epidermal growth factor (cbEGF)-like motifs (Faivre et al. 2008). Here we describe a case of Marfan syndrome in a patient who is a carrier of a novel de novo nonsense mutation in the FBN1 gene. Interestingly, the patient presented with only few clinical features of Marfan syndrome.