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

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, Ch.; Hillmer, A.M.; Wattanasirichaigoon, D.; Lyonnet, S.; Magdinier, F.; Javed, A.; Blewitt, M.E.; Amiel, J.; Wollnik, B.; Reversade, B.

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

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Item Type:	Article
Title:	De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development
Creators Name:	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, Ch., Hillmer, A.M., Wattanasirichaigoon, D., Lyonnet, S., Magdinier, F., Javed, A., Blewitt, M.E., Amiel, J., Wollnik, B. and Reversade, B.
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.
Keywords:	Cell Line, Choanal Atresia, Facioscapulohumeral Muscular Dystrophy, Genetic Epigenesis, Genetic Predisposition to Disease, Inbred C57BL Mice, Microphthalmos, Missense Mutation, Non-Histone Chromosomal Proteins, Nose, Animals, Mice, Xenopus laevis
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	49
Number:	2
Page Range:	249-255
Date:	February 2017
Official Publication:	https://doi.org/10.1038/ng.3765
PubMed:	View item in PubMed
Related to:	URL URL Type https://ega-archive.org/datasets/EGAD00001003130 External Dataset

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