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

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 lect...

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Main Authors: Mustafa M Munye, Anna Diaz-Font, Louise Ocaka, Maiken L Henriksen, Melissa Lees, Angela Brady, Dagan Jenkins, Jenny Morton, Soren W Hansen, Chiara Bacchelli, Philip L Beales, Victor Hernandez-Hernandez
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-03-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006679&type=printable
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author Mustafa M Munye
Anna Diaz-Font
Louise Ocaka
Maiken L Henriksen
Melissa Lees
Angela Brady
Dagan Jenkins
Jenny Morton
Soren W Hansen
Chiara Bacchelli
Philip L Beales
Victor Hernandez-Hernandez
author_facet Mustafa M Munye
Anna Diaz-Font
Louise Ocaka
Maiken L Henriksen
Melissa Lees
Angela Brady
Dagan Jenkins
Jenny Morton
Soren W Hansen
Chiara Bacchelli
Philip L Beales
Victor Hernandez-Hernandez
author_sort Mustafa M Munye
collection DOAJ
description 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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spelling doaj-art-d4cff8dee67f4df98f85d62b08e489052025-08-20T02:03:16ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-03-01133e100667910.1371/journal.pgen.1006679COLEC10 is mutated in 3MC patients and regulates early craniofacial development.Mustafa M MunyeAnna Diaz-FontLouise OcakaMaiken L HenriksenMelissa LeesAngela BradyDagan JenkinsJenny MortonSoren W HansenChiara BacchelliPhilip L BealesVictor Hernandez-Hernandez3MC 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006679&type=printable
spellingShingle Mustafa M Munye
Anna Diaz-Font
Louise Ocaka
Maiken L Henriksen
Melissa Lees
Angela Brady
Dagan Jenkins
Jenny Morton
Soren W Hansen
Chiara Bacchelli
Philip L Beales
Victor Hernandez-Hernandez
COLEC10 is mutated in 3MC patients and regulates early craniofacial development.
PLoS Genetics
title COLEC10 is mutated in 3MC patients and regulates early craniofacial development.
title_full COLEC10 is mutated in 3MC patients and regulates early craniofacial development.
title_fullStr COLEC10 is mutated in 3MC patients and regulates early craniofacial development.
title_full_unstemmed COLEC10 is mutated in 3MC patients and regulates early craniofacial development.
title_short COLEC10 is mutated in 3MC patients and regulates early craniofacial development.
title_sort colec10 is mutated in 3mc patients and regulates early craniofacial development
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006679&type=printable
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