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

Issued Date

2017-01-31

Resource Type

Article

ISSN

15461718
10614036

DOI

10.1038/ng.3765

Other identifier(s)

2-s2.0-85008686533

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Genetics. Vol.49, No.2 (2017), 249-255

Suggested Citation

Christopher T. Gordon, Shifeng Xue, Gökhan Yigit, Hicham Filali, Kelan Chen, Nadine Rosin, Koh Ichiro Yoshiura, Myriam Oufadem, Tamara J. Beck, Ruth McGowan, Alex C. Magee, Janine Altmüller, Camille Dion, Holger Thiele, Alexandra D. Gurzau, Peter Nürnberg, Dieter Meschede, Wolfgang Mühlbauer, 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 Nitschké, Nicola Ragge, Nicolas Lévy, Gökhan Tunçbilek, Audrey S.M. Teo, Michael L. Cunningham, Abdelaziz Sefiani, Hülya Kayserili, James M. Murphy, Chalermpong Chatdokmaiprai, Axel M. Hillmer, Duangrurdee Wattanasirichaigoon, Stanislas Lyonnet, Frédérique Magdinier, Asif Javed, Marnie E. Blewitt, Jeanne Amiel, Bernd Wollnik, Bruno Reversade De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development. Nature Genetics. Vol.49, No.2 (2017), 249-255. doi:10.1038/ng.3765 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41957

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Title

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

Author(s)

Christopher T. Gordon
 Shifeng Xue
 Gökhan Yigit
 Hicham Filali
 Kelan Chen
 Nadine Rosin
 Koh Ichiro Yoshiura
 Myriam Oufadem
 Tamara J. Beck
 Ruth McGowan
 Alex C. Magee
 Janine Altmüller
 Camille Dion
 Holger Thiele
 Alexandra D. Gurzau
 Peter Nürnberg
 Dieter Meschede
 Wolfgang Mühlbauer
 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 Nitschké
 Nicola Ragge
 Nicolas Lévy
 Gökhan Tunçbilek
 Audrey S.M. Teo
 Michael L. Cunningham
 Abdelaziz Sefiani
 Hülya Kayserili
 James M. Murphy
 Chalermpong Chatdokmaiprai
 Axel M. Hillmer
 Duangrurdee Wattanasirichaigoon
 Stanislas Lyonnet
 Frédérique Magdinier
 Asif Javed
 Marnie E. Blewitt
 Jeanne Amiel
 Bernd Wollnik
 Bruno Reversade

Other Contributor(s)

Inserm
 Universite Paris Descartes
 A-Star, Institute of Medical Biology
 A-Star, Institute of Molecular and Cell Biology
 Universitätsmedizin Göttingen
 Mohammed V University in Rabat
 Walter and Eliza Hall Institute of Medical Research
 University of Melbourne
 Nagasaki University
 Queen Elizabeth University Hospital
 Belfast Health and Social Care Trust
 University of Cologne
 Genetique Medicale et Genomique Fonctionnelle
 Institut für Humangenetik
 Facharzt fur plastische und asthetische Chirurgie
 Research Institute, Osaka Medical Center for Maternal and Child Health
 University Hospital of Wales
 Hopital La Timone
 NHS Foundation Trust
 University of Glasgow
 National Institute of Hygiene
 Helse Bergen Haukeland University Hospital
 Oxford Brookes University
 Hacettepe Üniversitesi
 A-Star, Genome Institute of Singapore
 University of Washington School of Medicine
 Koç Üniversitesi
 Mahidol University
 Hôpital Necker Enfants Malades
 National University of Singapore
 VU University Medical Center

Abstract

© 2017 Nature America, Inc. All rights reserved. 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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/41957

Collections

Scopus 2016-2017