Classic, atypically severe and neonatal Marfan syndrome: Twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40

Frank Tiecke, Stefanie Katzke, Patrick Booms, Peter N. Robinson, Luitgard Neumann, Maurice Godfrey, Kurt R. Mathews, Maren Scheuner, Georg Klaus Hinkel, Rolf E. Brenner, Hedwig H. Hövels-Gürich, Christian Hagemeier, Josefine Fuchs, Flemming Skovby, Thomas Rosenberg

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. There is a remarkable degree of clinical variability both within and between families with Marfan syndrome as well as in individuals with related disorders of connective tissue caused by FBN1 mutations and collectively termed type-1 fibrillinopathies. The so-called neonatal region in FBN1 exons 24-32 comprises one of the few generally accepted genotype-phenotype correlations described to date. In this work, we report 12 FBN1 mutations identified by temperature-gradient gel electrophoresis screening of exons 24-40 in 127 individuals with Marfan syndrome or related disorders. The data reported here, together with other published reports, document a significant clustering of mutations in exons 24-32. Although all reported mutations associated with neonatal Marfan syndrome and the majority of point mutations associated with atypically severe presentations have been found in exons 24-32, mutations associated with classic Marfan syndrome occur in this region as well. It is not possible to predict whether a given mutation in exons 24-32 will be associated with classic, atypically severe, or neonatal Marfan syndrome.

Original languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalEuropean Journal of Human Genetics
Volume9
Issue number1
DOIs
StatePublished - 2001

Keywords

  • Fibrillin
  • Genotype-phenotype correlation
  • Marfan syndrome
  • Temperature-gradient gel electrophoresis (TGGE)

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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