Table 2.

Criteria for causal FBN1 mutation [11]

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