Analysis of Ellis van Creveld syndrome gene products: implications for cardiovascular development and disease. Hum Mol Genet 2009 May 15;18(10):1813-24
Date
03/03/2009Pubmed ID
19251731Pubmed Central ID
PMC2671989DOI
10.1093/hmg/ddp098Scopus ID
2-s2.0-65449147041 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
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.
Author List
Sund KL, Roelker S, Ramachandran V, Durbin L, Benson DWMESH terms used to index this publication - Major topics in bold
AnimalsCardiovascular Diseases
Cohort Studies
Ellis-Van Creveld Syndrome
Female
Gene Expression
Heart
Humans
Intercellular Signaling Peptides and Proteins
Male
Membrane Proteins
Mice
Mice, Inbred C57BL
Mutation
Myocardium
NIH 3T3 Cells
Proteins
