MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates

Nat Genet. 2015 Nov;47(11):1260-3. doi: 10.1038/ng.3376. Epub 2015 Oct 5.

Abstract

Heterotaxy results from a failure to establish normal left-right asymmetry early in embryonic development. By whole-exome sequencing, whole-genome sequencing and high-throughput cohort resequencing, we identified recessive mutations in MMP21 (encoding matrix metallopeptidase 21) in nine index cases with heterotaxy. In addition, Mmp21-mutant mice and mmp21-morphant zebrafish displayed heterotaxy and abnormal cardiac looping, respectively, suggesting a new role for extracellular matrix remodeling in the establishment of laterality in vertebrates.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Family Health
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Recessive
  • Heart / embryology
  • Heart Defects, Congenital / genetics
  • Heterotaxy Syndrome / genetics*
  • Humans
  • In Situ Hybridization
  • Male
  • Matrix Metalloproteinases, Secreted / genetics*
  • Mice
  • Pedigree
  • Point Mutation*
  • Sequence Analysis, DNA / methods
  • Vertebrates / genetics*
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics

Substances

  • Zebrafish Proteins
  • MMP21 protein, human
  • Matrix Metalloproteinases, Secreted