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

Gordon, CT; Xue, S; Yigit, G; Filali, H; Chen, K; Rosin, N; Yoshiura, KI; Oufadem, M; Beck, TJ; McGowan, R; Magee, AC; Altmuller, J; Dion, C; Thiele, H; Gurzau, AD; Nurnberg, P; Meschede, D; Muhlbauer, W; Okamoto, N; Varghese, V; Irving, R; Sigaudy, S; Williams, D; Ahmed, SF; Bonnard, C; Kong, MK; Ratbi, I; Fejjal, N; Fikri, M; Elalaoui, SC; Reigstad, H; Bole-Feysot, C; Nitschke, P; Ragge, N; Levy, N; Tuncbilek, G; Teo, AS; Cunningham, ML; Sefiani, A; Kayserili, H; Murphy, JM; Chatdokmaiprai, C; Hillmer, AM; Wattanasirichaigoon, D; Lyonnet, S; Magdinier, F; Javed, A; Blewitt, ME; Amiel, J; Wollnik, B; Reversade, B

Author(s): Gordon, CT; Xue, S; Yigit, G; Filali, H; Chen, K; Rosin, N; Yoshiura, KI; Oufadem, M; Beck, TJ; McGowan, R; Magee, AC; Altmuller, J; Dion, C; Thiele, H; Gurzau, AD; Nurnberg, P; Meschede, D; Muhlbauer, W; Okamoto, N; Varghese, V; Irving, R; Sigaudy, S; Williams, D; Ahmed, SF; Bonnard, C; Kong, MK; Ratbi, I; Fejjal, N; Fikri, M; Elalaoui, SC; Reigstad, H; Bole-Feysot, C; Nitschke, P; Ragge, N; Levy, N; Tuncbilek, G; Teo, AS; Cunningham, ML; Sefiani, A; Kayserili, H; Murphy, JM; Chatdokmaiprai, C; Hillmer, AM; Wattanasirichaigoon, D; Lyonnet, S; Magdinier, F; Javed, A; Blewitt, ME; Amiel, J; Wollnik, B; Reversade, B;
Details: Publication Year 2017-02,Volume 49,Issue #2,Page 249-255
Journal Title: Nat Genet
Publication Type: Journal Article
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.
Publisher: Springer Nature
Research Division(s): Molecular Medicine; Cell Signalling And Cell Death
PubMed ID: 28067911
Publisher's Version: https://doi.org/10.1038/ng.3765
NHMRC Grants: NHMRC/1098290, NHMRC/1110206, NHMRC/1105754,
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Nat Genetics_Gordon et al_2017.pdf - (0.25MB, application/pdf)

Creation Date: 2017-04-06 09:27:44

Last Modified: 2018-01-16 09:42:41