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

Gordon, C. T. et al. (2017) De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development. Nature Genetics, 49, pp. 249-255. (doi: 10.1038/ng.3765) (PMID:28067911)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGowan, Ruth and Ahmed, Professor Syed Faisal
• Authors: Gordon, C. T., Xue, S., Yigit, G., Filali, H., Chen, K., Rosin, N., Yoshiura, K.-I., Oufadem, M., Beck, T. J., McGowan, R., Magee, A. C., Altmüller, J., Dion, C., Thiele, H., Gurzau, A. D., Nürnberg, P., Meschede, D., Mühlbauer, W., Okamoto, N., Varghese, V., Irving, R., Sigaudy, S., Williams, D., Ahmed, S. F., Bonnard, C., Kong, M. K., Ratbi, I., Fejjal, N., Fikri, M., Elalaoui, S. C., Reigstad, H., Bole-Feysot, C., Nitschké, P., Ragge, N., Lévy, N., Tunçbilek, G., Teo, A. S.M., Cunningham, M. L., Sefiani, A., Kayserili, H., Murphy, J. M., Chatdokmaiprai, C., Hillmer, A. M., Wattanasirichaigoon, D., Lyonnet, S., Magdinier, F., Javed, A., Blewitt, M. E., Amiel, J., Wollnik, B., and Reversade, B.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Copyright Holders: Copyright © 2017 Nature America Inc., part of Springer Nature
• First Published: First published in Nature Genetics 49(2):249-255
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher