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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Jul;57(1):8–21.

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

G Nijbroek 1, S Sood 1, I McIntosh 1, C A Francomano 1, E Bull 1, L Pereira 1, F Ramirez 1, R E Pyeritz 1, H C Dietz 1
PMCID: PMC1801235  PMID: 7611299

Abstract

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.

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Selected References

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