PUBLICATION
MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates
- Authors
- 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.
- ID
- ZDB-PUB-151006-2
- 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.
Citation
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. (2015) MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates. Nature Genetics. 47(11):1260-3.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping