From: The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome
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 |