Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons

Gaby Nijbroek, Sumesh Sood, Iain McIntosh, Clair A. Francomano, Evelyn Bull, Lygia Pereira, Francesco Ramirez, Reed E. Pyeritz, Harry C. Dietz

Research output: Contribution to journalArticlepeer-review

195 Scopus citations


Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause the Marfan syndrome (MFS). This statement is supported by the observations that the classic Marfan phenotype cosegregates with intragenic and/or flanking marker alleles in all families tested and that a significant number of FBN1 mutations have been identified in affected individuals. We have now devised a method to screen the entire coding sequence and flanking splice junctions of FBN1. On completion for a panel of nine probands with classic MFS, six new mutations were identified that accounted for disease in seven (78%) of nine patients. Nine additional new mutations have been characterized in the early stages of a larger screening project. These 15 mutations were equally distributed throughout the gene and, with one exception, were specific to single families. One-third of mutations created premature termination codons, and 6 of 15 substituted residues with putative significance for calcium binding to epidermal growth factor (EGF)- like domains. Mutations causing severe and rapidly progressive disease that presents in the neonatal period can occur in a larger region of the gene than previously demonstrated, and the nature of the mutation is as important a determinant as its location, in predisposing to this phenotype.

Original languageEnglish (US)
Pages (from-to)8-21
Number of pages14
JournalAmerican journal of human genetics
Issue number1
StatePublished - Jul 1995

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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