Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome
Open Access
- 23 January 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 43 (3), 197-203
- https://doi.org/10.1038/ng.757
Abstract
Phil Beales and colleagues show that mutations in the lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome, a disorder that includes craniofacial defects, learning disability and other developmental phenotypes. They also present evidence that the COLEC11 gene product serves as a guidance cue for neural crest cell migration. 3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.Keywords
This publication has 25 references indexed in Scilit:
- Collectin 11 (CL-11, CL-K1) Is a MASP-1/3–Associated Plasma Collectin with Microbial-Binding ActivityThe Journal of Immunology, 2010
- MASP1 Mutations in Patients with Facial, Umbilical, Coccygeal, and Auditory Findings of Carnevale, Malpuech, OSA, and Michels SyndromesAmerican Journal of Human Genetics, 2010
- Collective Chemotaxis Requires Contact-Dependent Cell PolarityDevelopmental Cell, 2010
- A Novel Mannose-binding Lectin/Ficolin-associated Protein Is Highly Expressed in Heart and Skeletal Muscle Tissues and Inhibits Complement ActivationOnline Journal of Public Health Informatics, 2010
- An agarose spot assay for chemotactic invasionBioTechniques, 2010
- Basal body stability and ciliogenesis requires the conserved component Poc1The Journal of cell biology, 2009
- MAp44, a Human Protein Associated with Pattern Recognition Molecules of the Complement System and Regulating the Lectin Pathway of Complement ActivationThe Journal of Immunology, 2009
- The receptor tyrosine kinase RET regulates hindgut colonization by sacral neural crest cellsDevelopmental Biology, 2008
- New perspectives on mannan-binding lectin-mediated complement activationImmunobiology, 2007
- A clefting syndrome with ocular anterior chamber defect and lid anomaliesThe Journal of Pediatrics, 1978