PUBLICATION

Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome

Authors
Rooryck, C., Diaz-Font, A., Osborn, D.P., Chabchoub, E., Hernandez-Hernandez, V., Shamseldin, H., Kenny, J., Waters, A., Jenkins, D., Kaissi, A.A., Leal, G.F., Dallapiccola, B., Carnevale, F., Bitner-Glindzicz, M., Lees, M., Hennekam, R., Stanier, P., Burns, A.J., Peeters, H., Alkuraya, F.S., and Beales, P.L.
ID
ZDB-PUB-110131-7
Date
2011
Source
Nature Genetics   43(3): 197-203 (Journal)
Registered Authors
Osborn, Dan
Keywords
none
MeSH Terms
  • Abnormalities, Multiple/genetics*
  • Animals
  • Cell Movement
  • Cleft Lip/genetics
  • Cleft Palate/genetics
  • Collectins/genetics*
  • Complement Pathway, Mannose-Binding Lectin/genetics*
  • Craniofacial Abnormalities/genetics*
  • Craniosynostoses/genetics
  • Epistasis, Genetic
  • Mannose-Binding Protein-Associated Serine Proteases/genetics*
  • Mutation
  • Neural Crest/cytology
  • Syndrome
  • Zebrafish
PubMed
21258343 Full text @ Nat. Genet.
Abstract
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes