Familial occurrence of typical and severe lethal congenital contractural arachnodactyly caused by missplicing of exon 34 of fibrillin-2

Am J Hum Genet. 1996 Nov;59(5):1027-34.


Genetic linkage studies have linked congenital contractural arachnodactyly (CCA), a usually mild heritable connective-tissue disorder, to FBN2, the fibrillin gene on chromosome 5. Recently, FBN2 mutations in two patients with CCA have been described. Here we report an A-->T transversion at the -2 position of the consensus acceptor splice site, resulting in the missplicing of exon 34, a calcium-binding epidermal growth factor-like repeat in fibrillin-2 in a mother and daughter with CCA. Significantly, the mother exhibited a classic CCA phenotype with arachnodactyly, joint contractures, and abnormal pinnae, whereas her daughter exhibited a markedly more severe CCA phenotype, which included cardiovascular and gastrointestinal anomalies that led to death in infancy. Analysis of cloned fibroblasts showed that the mother is a somatic mosaic for the exon 34 missplicing mutation, whereas all the daughter's cells harbored the mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Connective Tissue Diseases / congenital
  • Connective Tissue Diseases / genetics*
  • Connective Tissue Diseases / metabolism
  • Contracture / congenital
  • Contracture / genetics*
  • Contracture / metabolism
  • Exons / genetics
  • Female
  • Fibrillin-2
  • Fibrillins
  • Fibroblasts / metabolism
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Male
  • Microfilament Proteins / genetics*
  • Mutation
  • Polymerase Chain Reaction
  • Pregnancy


  • FBN2 protein, human
  • Fibrillin-2
  • Fibrillins
  • Microfilament Proteins