2. Academic Validation
  3. COLEC10 is mutated in 3MC patients and regulates early craniofacial development

COLEC10 is mutated in 3MC patients and regulates early craniofacial development

  • PLoS Genet. 2017 Mar 16;13(3):e1006679. doi: 10.1371/journal.pgen.1006679.
Mustafa M Munye 1,  Anna Diaz-Font 1,  Louise Ocaka 1,  Maiken L Henriksen 2,  Melissa Lees 3,  Angela Brady 4,  Dagan Jenkins 1,  Jenny Morton 5,  Soren W Hansen 2,  Chiara Bacchelli 1,  Philip L Beales 1,  Victor Hernandez-Hernandez 1
Affiliations

Affiliations

  • 1 Genetics and Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
  • 2 Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
  • 3 Department of Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.
  • 4 North West Thames Regional Genetics Service, Kennedy-Galton Centre, Northwick Park Hospital, London, United Kingdom.
  • 5 Department of Clinical Genetics, Birmingham Women's Hospital, Birmingham, United Kingdom.
PMID: 28301481 DOI: 10.1371/journal.pgen.1006679
Abstract

3MC syndrome is an autosomal recessive heterogeneous disorder with features linked to developmental abnormalities. The main features include facial dysmorphism, craniosynostosis and cleft lip/palate; skeletal structures derived from cranial neural crest cells (cNCC). We previously reported that lectin complement pathway genes COLEC11 and MASP1/3 are mutated in 3MC syndrome patients. Here we define a new gene, COLEC10, also mutated in 3MC families and present novel mutations in COLEC11 and MASP1/3 genes in a further five families. The protein products of COLEC11 and COLEC10, CL-K1 and CL-L1 respectively, form heteromeric complexes. We show COLEC10 is expressed in the base membrane of the palate during murine embryo development. We demonstrate how mutations in COLEC10 (c.25C>T; p.Arg9Ter, c.226delA; p.Gly77Glufs*66 and c.528C>G p.Cys176Trp) impair the expression and/or secretion of CL-L1 highlighting their pathogenicity. Together, these findings provide further evidence linking the lectin complement pathway and complement factors COLEC11 and COLEC10 to morphogenesis of craniofacial structures and 3MC etiology.

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