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Any of the following findings in an FBN1 screening should considered causal in making the diagnosis of Marfan syndrome. Marfan syndrome has been positively associated with each of the following:

• Mutation previously shown to segregate in Marfan family


• De novo (with proven paternity and absence of disease in parents) mutation (one of the five following categories


• Nonsense mutation


• Inframe and out of frame deletion/insertion


• Splice site mutations affecting canonical splice sequence or shown to alter splicing on mRNA/cDNA level


• Missense affecting/creating cysteine residues


• Missense affecting conserved residues of the EGF consensus sequence ((D/N)X(D/N)(E/Q)Xm(D/N)Xn(Y/F) with m and n representing variable number of residues; D aspartic acid, N asparagine, E glutamic acid, Q glutamine, Y tyrosine, F phenylalanine)


• Other missense mutations: segregation in family if possible + absence in 400 ethnically matched control chromosomes, if no family history absence in 400 ethnically matched control chromosomes


• Linkage of haplotype for n≥6 meioses to the FBN1 locus