| Literature DB >> 28067911 |
Christopher T Gordon1,2, Shifeng Xue3,4, Gökhan Yigit5, Hicham Filali1,2,6, Kelan Chen7,8, Nadine Rosin5, Koh-Ichiro Yoshiura9, Myriam Oufadem1,2, Tamara J Beck7, Ruth McGowan10, Alex C Magee11, Janine Altmüller12,13,14, Camille Dion15, Holger Thiele12, Alexandra D Gurzau7,8, Peter Nürnberg12,14,16, Dieter Meschede17, Wolfgang Mühlbauer18, Nobuhiko Okamoto19, Vinod Varghese20, Rachel Irving20, Sabine Sigaudy21, Denise Williams22, S Faisal Ahmed23, Carine Bonnard3, Mung Kei Kong3, Ilham Ratbi6, Nawfal Fejjal24, Meriem Fikri25, Siham Chafai Elalaoui6,26, Hallvard Reigstad27, Christine Bole-Feysot2,28, Patrick Nitschké2,29, Nicola Ragge22,30, Nicolas Lévy15,21, Gökhan Tunçbilek31, Audrey S M Teo32, Michael L Cunningham33, Abdelaziz Sefiani6,26, Hülya Kayserili34, James M Murphy7,8, Chalermpong Chatdokmaiprai35, Axel M Hillmer32, Duangrurdee Wattanasirichaigoon36, Stanislas Lyonnet1,2,37, Frédérique Magdinier15, Asif Javed32, Marnie E Blewitt7,8, Jeanne Amiel1,2,37, Bernd Wollnik5,13, Bruno Reversade3,4,34,38,39.
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.Entities:
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Year: 2017 PMID： 28067911 DOI： 10.1038/ng.3765
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330