Paucity of skeletal manifestations in Hispanic families with FBN1 mutations

Eur J Med Genet. Mar-Apr 2010;53(2):80-4. doi: 10.1016/j.ejmg.2009.11.001. Epub 2009 Nov 23.

Abstract

Marfan syndrome (MFS) is an autosomal dominant condition with pleiotropic manifestations involving the skeletal, ocular, and cardiovascular systems. The diagnosis is based primarily on clinical involvement of these and other systems, referred to as the Ghent criteria. We have identified three Hispanic families from Mexico with cardiovascular and ocular manifestations due to novel FBN1 mutations but with paucity of skeletal features. The largest family, hMFS001, had a frameshift mutation in exon 24 (3075delC) identified as the cause of aortic disease in the family. Assessment of eight affected adults revealed no major skeletal manifestation of MFS. Family hMFS002 had a missense mutation (R1530C) in exon 37. Four members fulfilled the criteria for ocular and cardiovascular phenotype but lacked skeletal manifestations. Family hMFS003 had two consecutive missense FBN1 mutations (C515W and R516G) in exon 12. Eight members fulfilled the ocular criteria for MFS and two members had major cardiovascular manifestations, however none of them met criteria for skeletal system. These data suggest that individuals of Hispanic descent with FBN1 mutations may not manifest skeletal features of the MFS to the same extent as Caucasians. We recommend that echocardiogram, ocular examination and FBN1 molecular testing be considered for any patients with possible MFS even in the absence of skeletal features, including Hispanic patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases / genetics
  • DNA Mutational Analysis
  • Exons
  • Family Health
  • Female
  • Fibrillin-1
  • Fibrillins
  • Humans
  • Male
  • Marfan Syndrome / ethnology
  • Marfan Syndrome / genetics*
  • Mexico
  • Microfilament Proteins / genetics*
  • Models, Genetic
  • Mutation
  • Mutation, Missense*
  • Pedigree
  • Phenotype

Substances

  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins