De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Christopher T. Gordon; Shifeng Xue; Goekhan Yigit; Hicham Filali; Kelan Chen; Nadine Rosins; Koh-ichiro Yoshiura; Myriam Oufadem; Tamara J. Beck; Ruth McGowan; Alex C. Magee; Janine Altmueller; Camille Dion; Holger Thiele; Alexandra D. Gurzau; Peter Nuernberg; Dieter Meschede; Wolfgang Muehlbauer; Nobuhiko Okamoto; Vinod Varghese; Rachel Irving; Sabine Sigaudy; Denise Williams; S. Faisal Ahmed; Carine Bonnard; Mung Kei Kong; Ilham Ratbi; Nawfal Fejjal; Meriem Fikri; Siham Chafai Elalaoui; Hallvard Reigstad; Christine Bole-Feysot; Patrick Nitschke; Nicola Ragge; Nicolas Levy; Goekhan Tuncbilek; Audrey S. M. Teo; Michael L. Cunningham; Abdelaziz Sefiani; Huelya Kayserili; James M. Murphy; Chalermpong Chatdokmaiprai; Axel M. Hillmer; Duangrurdee Wattanasirichaigoon; Stanislas Lyonnet; Frederique Magdinier; Asif Javed; Marnie E. Blewitt; Jeanne Amiel; Bernd Wollnik; Bruno Reversade

doi:10.1038/ng.3765

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De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Journal article

Peer reviewed

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Christopher T. Gordon, Shifeng Xue, Goekhan Yigit, Hicham Filali, Kelan Chen, Nadine Rosins, Koh-ichiro Yoshiura, Myriam Oufadem, Tamara J. Beck, Ruth McGowan, …

Nature genetics, Vol.49(2), pp.249-255

01/02/2017

DOI: https://doi.org/10.1038/ng.3765

PMID: 28067911

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD.

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Title: De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development
Creators - without role: Christopher T. Gordon - Inserm
Shifeng Xue - College Station Medical Center
Goekhan Yigit - College Station Medical Center
Hicham Filali - Inserm
Kelan Chen - College Station Medical Center
Nadine Rosins - College Station Medical Center
Koh-ichiro Yoshiura - Nagasaki University
Myriam Oufadem - Inserm
Tamara J. Beck
Ruth McGowan - Queen Elizabeth Univ Hosp, West Scotland Reg Genet Serv, Glasgow, Lanark, Scotland
Alex C. Magee - Northern (Arctic) Federal University
Janine Altmueller - University of Cologne
Camille Dion - Aix-Marseille University
Holger Thiele - University of Cologne
Alexandra D. Gurzau - College Station Medical Center
Peter Nuernberg - University of Cologne
Dieter Meschede
Wolfgang Muehlbauer - ATOS Klin Munchen, Plast & Asthet Chirurg, Munich, Germany
Nobuhiko Okamoto - College Station Medical Center
Vinod Varghese - University of Wales
Rachel Irving - University of Wales
Sabine Sigaudy - Assistance Publique – Hôpitaux de Paris
Denise Williams - Birmingham Womens NHS Fdn Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England
S. Faisal Ahmed - University of Glasgow
Carine Bonnard - College Station Medical Center
Mung Kei Kong - College Station Medical Center
Ilham Ratbi - Mohammed V University
Nawfal Fejjal - Mohammed V University
Meriem Fikri - Mohammed V University
Siham Chafai Elalaoui - Mohammed V University
Hallvard Reigstad - Intens
Christine Bole-Feysot - Sorbonne Paris Cité
Patrick Nitschke - Sorbonne Paris Cité
Nicola Ragge - Birmingham Womens NHS Fdn Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England
Nicolas Levy - Assistance Publique – Hôpitaux de Paris
Goekhan Tuncbilek - Hacettepe University
Audrey S. M. Teo - Genome Institute of Singapore
Michael L. Cunningham - University of Washington
Abdelaziz Sefiani - Mohammed V University
Huelya Kayserili - Koç University
James M. Murphy - College Station Medical Center
Chalermpong Chatdokmaiprai - Mahidol University
Axel M. Hillmer - Genome Institute of Singapore
Duangrurdee Wattanasirichaigoon - Mahidol University
Stanislas Lyonnet - Inserm
Frederique Magdinier
Asif Javed - Genome Institute of Singapore
Marnie E. Blewitt - College Station Medical Center
Jeanne Amiel - Inserm
Bernd Wollnik - College Station Medical Center
Bruno Reversade - College Station Medical Center
Publication Details: Nature genetics, Vol.49(2), pp.249-255
Publisher: Springer Nature
Number of pages: 7
Grant note: MACS Baillie Gifford grant 112S398 / Scientific and Technological Research Council of Turkey (TUBITAK); Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) Scientific and Technological Research Council of Turkey (TUBITAK) (E-RARE network CRANIRARE-2); Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) VICTA inaugural AAA Fellowship in Amsterdam ANR-10-IAHU-01 / Agence Nationale de la Recherche (CranioRespiro); Agence Nationale de la Recherche (ANR) Victorian State Government Operational Infrastructure Support AstarSTAR BMRC Young Investigator Grant MR/N003403/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Association Francaise contre les Myopathies (AFM); Association Francaise contre les Myopathies German Federal Ministry of Education and Research (BMBF) (E-RARE network CRANIRARE-2); Federal Ministry of Education & Research (BMBF) SFB1002 / German Research Foundation; German Research Foundation (DFG) 1098290; 1110206; 1105754 / National Health and Medical Research Council (NHMRC) of Australia Strategic Positioning Fund on Genetic Orphan Diseases from the Biomedical Research Council, AstarSTAR, Singapore INSERM; Institut National de la Sante et de la Recherche Medicale (Inserm) AstarSTAR JCO Career Development grant Cancer Council Victoria; Canadian Institutes of Health Research (CIHR) 9000220 / NHMRC TRUSS grant; National Health and Medical Research Council (NHMRC) of Australia 01GM1211A / German Federal Ministry of Education and Research (BMBF); Federal Ministry of Education & Research (BMBF) Jean Renny Endowed Chair for Craniofacial Research 16KT0112; 16H05159 / Grants-in-Aid for Scientific Research; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research (KAKENHI) French Ministry of Education and Research Faculty of Medicine Ramathibodi Hospital 1098290; 1110206 / National Health and Medical Research Council of Australia; National Health and Medical Research Council (NHMRC) of Australia
Identifiers: 9942172108331
Academic Unit: King Abdullah University of Science & Technology
Language: English
Resource Type: Journal article