ArticleJournal of medical genetics2015
A human laterality disorder caused by a homozygous deleterious mutation in MMP21.
Article in Journal of medical genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Genetics in Heterotaxy: A Case Series and Literature Review on DNAH9, PKD1L1, MMP21, and GDF1.Clinical genetics · 2026Pooled it
- Cytomegalovirus-encoded immediate early 1 protein perturbs neural progenitor proliferation via interfering with host PML-DISC1 interaction.The Journal of biological chemistry · 2026Article
- DISC1-PML protein interaction for congenital CMV infection-induced cortical neural progenitor deficit: perturbance of host signaling via viral IE1.bioRxiv : the preprint server for biology · 2025Article
- Molecular adaptations in MMP genes support lung elasticity and diving adaptations in cetaceans.BMC genomics · 2025Article
- Ultrasound detection of biliary atresia splenic malformation syndrome from prenatal to postnatal: a case description.Quantitative imaging in medicine and surgery · 2025Article
- CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.American journal of human genetics · 2025Article
- Locally invasive cholangiocarcinoma causing gastric outlet obstruction in heterotaxy syndrome: A case report and review of literature.Radiology case reports · 2024Article
- Human Genetics of Defects of Situs.Advances in experimental medicine and biology · 2024Review
- Wnt activation disturbs cell competition and causes diffuse invasion of transformed cells through NF-κB-MMP21 pathway.Nature communications · 2023Article
- Overlapping pathogenic de novo CNVs in neurodevelopmental disorders and congenital anomalies impacting constraint genes regulating early development.Human genetics · 2023Article
- Identification of novel compound heterozygous variants in theFrontiers in molecular biosciences · 2023Article
- A minimally invasive fin scratching protocol for fast genotyping and early selection of zebrafish embryos.Scientific reports · 2022Article
- De novo disruptive heterozygous MMP21 variants are potential predisposing genetic risk factors in Chinese Han heterotaxy children.Human genomics · 2022Article
- Mutation spectrum of congenital heart disease in a consanguineous Turkish population.Molecular genetics & genomic medicine · 2022Article
- Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates.Nature genetics · 2022Article
- Unusual long survival in a case of heterotaxy and polysplenia.Surgical and radiologic anatomy : SRA · 2021Article
- Role of cilia in the pathogenesis of congenital heart disease.Seminars in cell & developmental biology · 2021Review
- Article
- Identification of aExperimental and therapeutic medicine · 2020Article
- A fully-automated method discovers loss of mouse-lethal and human-monogenic disease genes in 58 mammals.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundLaterality in the vertebrate embryo is determined by left-right asymmetric gene expression driven by the flow of extraembryonic fluid across the embryonic node. Defects in these processes cause heterotaxy, the abnormal formation and arrangement of visceral organs that can range from complete inversion of symmetry to the selective misarrangement of organs. However, our understanding of the genetic causality for laterality defects in human beings remains relatively limited.
methodsWe performed whole exome sequencing in a consanguineous family with heterotaxia. To interrogate the pathogenic potential of the discovered variant, we used an in vivo system in which the potential of the candidate gene to induce L-R asymmetry was tested by transient suppression and CRISPR/Cas9-induced deletions. We also used in vitro assays to test a possible link between our exome-derived candidate and Notch signaling.
resultsWe identified a homozygous 2 bp deletion in MMP21, encoding matrix metalloproteinase-21, as the sole coding mutation that segregated with the phenotype. Transient suppression or CRISPR/Cas9-mediated deletion of mmp21 in zebrafish embryos induced cardiac looping defects, with concomitant disruption of laterality markers in the lateral plate mesoderm and disrupted notch signalling in vitro and in vivo.
conclusionsOur data implicate loss of MMP21 as a cause of heterotaxy in humans with concomitant defects in Notch signaling. In support of this finding, a homozygous missense mutation in MMP21 was identified previously in mice with N-Ethyl-N-Nitrosourea (ENU)-induced heterotaxy. Taken together, these observations suggest a role of matrix metalloproteinases in the establishment of asymmetric organ development, likely through the regulation of morphogenetic signals.
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