Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects

Am J Hum Genet. 2003 Apr;72(4):1047-52. doi: 10.1086/374319. Epub 2003 Mar 11.


Atrioventricular septal defects (AVSD) are common cardiovascular malformations, occurring in 3.5/10,000 births. Although frequently associated with trisomy 21, autosomal dominant AVSD has also been described. Recently we identified and characterized the cell adhesion molecule CRELD1 (previously known as "cirrin") as a candidate gene for the AVSD2 locus mapping to chromosome 3p25. Analysis of the CRELD1 gene from individuals with non-trisomy 21-associated AVSD identified heterozygous missense mutations in nearly 6% of this population, including mutations in isolated AVSD and AVSD associated with heterotaxy syndrome. CRELD1 is the first human gene to be implicated in the pathogenesis of isolated AVSD and AVSD in the context of heterotaxy, which provides an important step in unraveling the pathogenesis of AVSD.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 21 / genetics
  • Chromosomes, Human, Pair 3* / genetics
  • Down Syndrome / genetics
  • Epidermal Growth Factor / genetics
  • Exons / genetics
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / genetics*
  • Heart Septal Defects, Atrial / genetics*
  • Heart Septal Defects, Ventricular / genetics*
  • Heterozygote
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • CRELD1 protein, human
  • Cell Adhesion Molecules
  • Extracellular Matrix Proteins
  • Epidermal Growth Factor

Associated data

  • GENBANK/AF452623
  • OMIM/208530
  • OMIM/214800
  • OMIM/225500
  • OMIM/236700
  • OMIM/605376
  • OMIM/606217