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

Caroline Rooryck, Anna Diaz-Font, Daniel P S Osborn, Elyes Chabchoub, Victor Hernandez-Hernandez, Hanan Shamseldin, Joanna Kenny, Aoife Waters, Dagan Jenkins, Ali Al Kaissi, Gabriela F. Leal, Bruno Dallapiccola, Franco Carnevale, Maria Bitner-Glindzicz, Melissa Lees, Raoul Hennekam, Philip Stanier, Alan J. Burns, Hilde Peeters, Fowzan S. AlkurayaPhilip L. Beales

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)197-203
Number of pages7
JournalNature Genetics
Issue number3
Publication statusPublished - Mar 2011

ASJC Scopus subject areas

  • Genetics


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