MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates.
Anne GuimierGeorge C GabrielFanny BajolleMichael TsangHui LiuAaron NollMolly SchwartzRajae El MaltiLaurie D SmithNikolai T KlenaGina JimenezNeil A MillerMyriam OufademAnne Moreau de BellaingHisato YagiCarol J SaundersCandice N BakerSylvie Di FilippoKevin A PetersonIsabelle ThiffaultChristine Bole-FeysotLinda D CooleyEmily G FarrowCécile MassonPatric SchoenJean-François DeleuzePatrick NitschkéStanislas LyonnetLoic de PontualStephen A MurrayDamien BonnetStephen F KingsmoreJeanne AmielPatrice BouvagnetCecilia W LoChristopher T GordonPublished in: Nature genetics (2015)
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.