MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates.
Guimier A,Gabriel G,Bajolle F,Tsang M,Liu H,Noll A,Schwartz M,El Malti R,Smith L,Klena N,Jimenez G,Miller N,Oufadem M,Moreau de Bellaing A,Yagi H,Saunders C,Baker C,Di Filippo S,Peterson K,Thiffault I,Bole-Feysot C,Cooley L,Farrow E,Masson C,Schoen P,Deleuze J,Nitschké P,Lyonnet S,de Pontual L,Murray S,Bonnet D,Kingsmore S,Amiel J,Bouvagnet P,Lo C,Gordon C
Source :
Nat. Genet.
2015 Oct 5
Pmid / DOI:
26437028
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.