Evidence by expression analysis of candidate genes for congenital heart defects in the NF1 microdeletion interval

Ann Hum Genet. 2005 Sep;69(Pt 5):508-16. doi: 10.1111/j.1529-8817.2005.00203.x.


It was recently reported that congenital heart disease is significantly more frequent in patients with NF1 microdeletion syndrome than in those with classical NF1. The outcome of congenital heart disease in this subset of patients is likely caused by the haploinsufficiency of gene/s in the deletion interval. Following in silico analysis of the deleted region, we found two genes known to be expressed in adult heart, the Joined to JAZF1 (SUZ12) and the Centaurin-alpha 2 (CENTA2) genes, and seven other genes with poorly defined patterns of expression and function. With the aim of defining their expression profiles in human fetal tissues (15th-21st weeks of gestation), expression analysis by RT-PCR and Northern blotting was performed. C17orf40, SUZ12 and CENTA2 were found to be mainly expressed in fetal heart, and following RT-PCR on mouse embryos and embryonic heart and brain at different stages of development, we found that the orthologous genes C17orf40, Suz12 and Centa2 are also expressed in early stages of development, before and during the formation of the four heart chambers. The presence of binding sites for Nkx2-5, a transcription factor expressed early in heart development, in all three mouse orthologous genes was predicted by bioinformatics, thus reinforcing the hypothesis that these genes might be involved in heart development and may be plausible candidates for congenital heart disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Blotting, Northern
  • Computational Biology
  • DNA Primers / chemistry
  • Databases, Factual
  • Gene Deletion*
  • Gene Expression Regulation
  • Gene Expression Regulation, Developmental*
  • Genes, Neurofibromatosis 1*
  • Heart
  • Heart Defects, Congenital / genetics*
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / metabolism
  • Humans
  • Mice
  • Mutation
  • Myocardium / metabolism
  • Neurofibromin 1 / genetics*
  • Phenotype
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Distribution
  • Transcription Factors / metabolism


  • DNA Primers
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • NKX2-5 protein, human
  • Neurofibromin 1
  • RNA, Messenger
  • Transcription Factors