Munye, MM;
Diaz-Font, A;
Ocaka, L;
Henriksen, ML;
Lees, M;
Brady, A;
Jenkins, D;
... Hernandez-Hernandez, V; + view all
(2017)
COLEC10 is mutated in 3MC patients and regulates early craniofacial development.
PLoS Genet
, 13
(3)
, Article e1006679. 10.1371/journal.pgen.1006679.
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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.
| Type: | Article |
|---|---|
| Title: | COLEC10 is mutated in 3MC patients and regulates early craniofacial development |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pgen.1006679 |
| Publisher version: | https://doi.org/10.1371/journal.pgen.1006679 |
| Language: | English |
| Additional information: | © 2017 Munye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, Collectin Liver 1, Pattern-Recognition Molecules, Lectin Complement Pathway, Neural Crest, Cell-Migration, OSA Syndrome, Activation, Mechanisms, Mutations, Complexes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1551463 |
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