دورية أكاديمية
أعرض في EDS

Identification of a novel variant of the ciliopathic gene FUZZY associated with craniosynostosis.

التفاصيل البيبلوغرافية
العنوان: Identification of a novel variant of the ciliopathic gene FUZZY associated with craniosynostosis.
المؤلفون: Barrell WB; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK., Adel Al-Lami H; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK.; Department of Orthodontics, College of Dentistry, University of Baghdad, Baghdad, Iraq., Goos JAC; Department of Plastic and Reconstructive Surgery and Hand Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands., Swagemakers SMA; Department of Bioinformatics, Erasmus University Medical Centre, Rotterdam, The Netherlands., van Dooren M; Department of Plastic and Reconstructive Surgery and Hand Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands.; Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands., Torban E; Department of Medicine, McGill University Health Centre, Montreal, Canada., van der Spek PJ; Department of Bioinformatics, Erasmus University Medical Centre, Rotterdam, The Netherlands., Mathijssen IMJ; Department of Plastic and Reconstructive Surgery and Hand Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands., Liu KJ; Centre for Craniofacial and Regenerative Biology, King's College London, London, SE1 9RT, UK. karen.liu@kcl.ac.uk.
المصدر: European journal of human genetics : EJHG [Eur J Hum Genet] 2022 Mar; Vol. 30 (3), pp. 282-290. Date of Electronic Publication: 2021 Nov 01.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9302235 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5438 (Electronic) Linking ISSN: 10184813 NLM ISO Abbreviation: Eur J Hum Genet Subsets: MEDLINE
أسماء مطبوعة: Publication: <2003->: London : Nature Publishing Group
Original Publication: Basel ; New York : Karger, [1992-
مواضيع طبية MeSH: Craniosynostoses*/diagnosis , Craniosynostoses*/genetics , Hedgehog Proteins*/genetics , Hedgehog Proteins*/metabolism, Cytoskeletal Proteins/*genetics , Intracellular Signaling Peptides and Proteins/*genetics, Animals ; Fibroblasts/metabolism ; Humans ; Mice
مستخلص: Craniosynostosis is a birth defect occurring in approximately one in 2000 live births, where premature fusion of the cranial bones inhibits growth of the skull during critical periods of brain development. The resulting changes in skull shape can lead to compression of the brain, causing severe complications. While we have some understanding of the molecular pathology of craniosynostosis, a large proportion of cases are of unknown genetic aetiology. Based on studies in mouse, we previously proposed that the ciliopathy gene Fuz should be considered a candidate craniosynostosis gene. Here, we report a novel variant of FUZ (c.851 G > C, p.(Arg284Pro)) found in monozygotic twins presenting with craniosynostosis. To investigate whether Fuz has a direct role in regulating osteogenic fate and mineralisation, we cultured primary osteoblasts and mouse embryonic fibroblasts (MEFs) from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation. This suggests that FUZ protein normally acts as a negative regulator of osteogenesis. We then used Fuz mutant MEFs, which lose functional primary cilia, to test whether the FUZ p.(Arg284Pro) variant could restore FUZ function during ciliogenesis. We found that expression of the FUZ p.(Arg284Pro) variant was sufficient to partially restore cilia numbers, but did not mediate a comparable response to Hedgehog pathway activation. Together, this suggests the osteogenic effects of FUZ p.(Arg284Pro) do not depend upon initiation of ciliogenesis.
(© 2021. The Author(s).)
References: Nat Protoc. 2015 Jun;10(6):845-58. (PMID: 25950237)
Development. 1997 Oct;124(20):4029-37. (PMID: 9374400)
Int J Oral Sci. 2015 Jun 26;7(2):73-9. (PMID: 26023726)
Eur J Hum Genet. 2011 Apr;19(4):369-76. (PMID: 21248745)
J Cell Sci. 2015 Dec 1;128(23):4263-72. (PMID: 26567219)
Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772)
Dev Cell. 2008 May;14(5):674-88. (PMID: 18477451)
Am J Med Genet A. 2010 Dec;152A(12):2995-3006. (PMID: 21108387)
Nat Genet. 2006 Mar;38(3):303-11. (PMID: 16493421)
Curr Opin Pediatr. 2017 Dec;29(6):622-628. (PMID: 28914635)
Cell. 2016 May 5;165(4):1002-11. (PMID: 27114037)
Cold Spring Harb Perspect Biol. 2017 May 1;9(5):. (PMID: 27881449)
Genesis. 2011 Oct;49(10):784-96. (PMID: 21557453)
Nat Cell Biol. 2009 Oct;11(10):1225-32. (PMID: 19767740)
Front Mol Neurosci. 2019 Jun 21;12:139. (PMID: 31293383)
Curr Top Dev Biol. 2008;85:303-32. (PMID: 19147010)
Curr Genet Med Rep. 2014 Sep 1;2(3):135-145. (PMID: 26146596)
Trends Biochem Sci. 2004 Dec;29(12):682-8. (PMID: 15544955)
Biochem Soc Trans. 2016 Dec 15;44(6):1753-1759. (PMID: 27913686)
Nat Rev Mol Cell Biol. 2011 Apr;12(4):222-34. (PMID: 21427764)
Hum Mol Genet. 2011 Nov 15;20(22):4324-33. (PMID: 21840926)
JCO Clin Cancer Inform. 2020 Mar;4:310-317. (PMID: 32228266)
Hum Mutat. 2000;15(1):7-12. (PMID: 10612815)
J Cell Biol. 2018 Jan 2;217(1):413-427. (PMID: 29038301)
J Craniomaxillofac Surg. 2016 Sep;44(9):1273-9. (PMID: 27499511)
Rare Dis. 2013 Nov 11;1:e27109. (PMID: 25003013)
Cold Spring Harb Perspect Biol. 2017 Sep 1;9(9):. (PMID: 28213462)
Nucleic Acids Res. 2010 Sep;38(16):e164. (PMID: 20601685)
J Cell Biol. 2012 Jul 9;198(1):37-45. (PMID: 22778277)
Am J Med Genet. 1995 Feb 13;55(4):500-4. (PMID: 7762595)
Nat Genet. 2016 Jun;48(6):648-56. (PMID: 27158779)
Genes Dis. 2014 Sep;1(1):120-125. (PMID: 25426492)
Genes Dev. 1999 Aug 15;13(16):2072-86. (PMID: 10465785)
J Am Chem Soc. 2002 Dec 11;124(49):14520-1. (PMID: 12465946)
Dev Biol. 2016 Sep 1;417(1):4-10. (PMID: 27395007)
Bioinformatics. 2020 Feb 15;36(4):990-993. (PMID: 31562761)
Science. 2010 Jan 1;327(5961):78-81. (PMID: 19892942)
Dev Cell. 2013 Jun 24;25(6):623-35. (PMID: 23806618)
J Cell Biol. 1993 Oct;123(1):209-21. (PMID: 8408199)
Curr Biol. 2019 Oct 7;29(19):3323-3330.e8. (PMID: 31564489)
PLoS One. 2011;6(9):e24608. (PMID: 21935430)
Hum Mutat. 2018 Jan;39(1):152-166. (PMID: 29068549)
معلومات مُعتمدة: MC_PC_21044 United Kingdom MRC_ Medical Research Council; MC_PC_21047 United Kingdom MRC_ Medical Research Council; BB/R015953/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council
المشرفين على المادة: 0 (Cytoskeletal Proteins)
0 (Fuz protein, mouse)
0 (Hedgehog Proteins)
0 (Intracellular Signaling Peptides and Proteins)
تواريخ الأحداث: Date Created: 20211101 Date Completed: 20220502 Latest Revision: 20240320
رمز التحديث: 20240320
مُعرف محوري في PubMed: PMC8904458
DOI: 10.1038/s41431-021-00988-6
PMID: 34719684
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5438
DOI:10.1038/s41431-021-00988-6