Analysis of Ellis van Creveld syndrome gene products: implications for cardiovascular development and disease

Hum Mol Genet. 2009 May 15;18(10):1813-24. doi: 10.1093/hmg/ddp098. Epub 2009 Feb 27.


Mutations identified in a cohort of patients with atrioventricular septal defects as a part of Ellis van Creveld syndrome (EvC syndrome) led us to study the role of two non-homologous genes, EVC and LBN, in heart development and disease pathogenesis. To address the cause of locus heterogeneity resulting in an indistinguishable heart-hand phenotype, we carried out in situ hybridization and immunofluorescence and identified co-localization of Evc and Lbn mRNA and protein. In the heart, expression was identified to be strongest in the secondary heart field, including both the outflow tract and the dorsal mesenchymal protrusion, but was also found in mesenchymal structures of the atrial septum and the atrioventricular cushions. Finally, we studied the transcriptional hierarchy of EVC and LBN but did not find any evidence of direct transcriptional interregulation between the two. Due to the locus heterogeneity of human mutations predicted to result in a loss of protein function, a bidirectional genomic organization and overlapping expression patterns, we speculate that these proteins function coordinately in cardiac development and that loss of this coordinate function results in the characteristics of EvC syndrome.

Publication types

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

MeSH terms

  • Animals
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Cohort Studies
  • Ellis-Van Creveld Syndrome / genetics*
  • Ellis-Van Creveld Syndrome / metabolism
  • Female
  • Gene Expression
  • Heart / growth & development*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Myocardium / metabolism
  • NIH 3T3 Cells
  • Proteins / genetics*
  • Proteins / metabolism


  • EVC protein, human
  • EVC2 protein, human
  • EVC2 protein, mouse
  • Evc protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Proteins