ZFIN ID: ZDB-PUB-151006-2
MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates
Guimier, A., Gabriel, G.C., Bajolle, F., Tsang, M., Liu, H., Noll, A., Schwartz, M., El Malti, R., Smith, L.D., Klena, N.T., Jimenez, G., Miller, N.A., Oufadem, M., Moreau de Bellaing, A., Yagi, H., Saunders, C.J., Baker, C.N., Di Filippo, S., Peterson, K.A., Thiffault, I., Bole-Feysot, C., Cooley, L.D., Farrow, E.G., Masson, C., Schoen, P., Deleuze, J.F., Nitschké, P., Lyonnet, S., de Pontual, L., Murray, S.A., Bonnet, D., Kingsmore, S.F., Amiel, J., Bouvagnet, P., Lo, C.W., Gordon, C.T.
Date: 2015
Source: Nature Genetics   47(11): 1260-3 (Journal)
Registered Authors: Lo, Cecilia, Tsang, Michael
Keywords: Medical genetics, Organogenesis
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
PubMed: 26437028 Full text @ Nat. Genet.
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.