Медицинская библиотека · Nature genetics · 2017

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

Gordon Christopher T, Xue Shifeng, Yigit Gökhan, Filali Hicham, Chen Kelan, Rosin Nadine, Yoshiura Koh-Ichiro, Oufadem Myriam, Beck Tamara J, McGowan Ruth, Magee Alex C, Altmüller Janine, Dion Camille, Thiele Holger, Gurzau Alexandra D, Nürnberg Peter, Meschede Dieter, Mühlbauer Wolfgang, Okamoto Nobuhiko, Varghese Vinod, Irving Rachel, Sigaudy Sabine, Williams Denise, Ahmed S Faisal, Bonnard Carine, Kong Mung Kei, Ratbi Ilham, Fejjal Nawfal, Fikri Meriem, Elalaoui Siham Chafai, Reigstad Hallvard, Bole-Feysot Christine, Nitschké Patrick, Ragge Nicola, Lévy Nicolas, Tunçbilek Gökhan, Teo Audrey S M, Cunningham Michael L, Sefiani Abdelaziz, Kayserili Hülya, Murphy James M, Chatdokmaiprai Chalermpong, Hillmer Axel M, Wattanasirichaigoon Duangrurdee, Lyonnet Stanislas, Magdinier Frédérique, Javed Asif, Blewitt Marnie E, Amiel Jeanne, Wollnik Bernd, Reversade Bruno

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Аннотация

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.

Для цитирования: Gordon Christopher T, Xue Shifeng, Yigit Gökhan, Filali Hicham, Chen Kelan, Rosin Nadine, Yoshiura Koh-Ichiro, Oufadem Myriam, Beck Tamara J, McGowan Ruth, Magee Alex C, Altmüller Janine, Dion Camille, Thiele Holger, Gurzau Alexandra D, Nürnberg Peter, Meschede Dieter, Mühlbauer Wolfgang, Okamoto Nobuhiko, Varghese Vinod, Irving Rachel, Sigaudy Sabine, Williams Denise, Ahmed S Faisal, Bonnard Carine, Kong Mung Kei, Ratbi Ilham, Fejjal Nawfal, Fikri Meriem, Elalaoui Siham Chafai, Reigstad Hallvard, Bole-Feysot Christine, Nitschké Patrick, Ragge Nicola, Lévy Nicolas, Tunçbilek Gökhan, Teo Audrey S M, Cunningham Michael L, Sefiani Abdelaziz, Kayserili Hülya, Murphy James M, Chatdokmaiprai Chalermpong, Hillmer Axel M, Wattanasirichaigoon Duangrurdee, Lyonnet Stanislas, Magdinier Frédérique, Javed Asif, Blewitt Marnie E, Amiel Jeanne, Wollnik Bernd, Reversade Bruno. De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development.. Nature genetics. 2017. DOI: 10.1038/ng.3765.

Предметные рубрики MeSH

Animals Cell Line Child, Preschool Choanal Atresia Chromosomal Proteins, Non-Histone Epigenesis, Genetic Female Genetic Predisposition to Disease Humans Male Mice Mice, Inbred C57BL Microphthalmos Muscular Dystrophy, Facioscapulohumeral Mutation, Missense Nose Xenopus laevis

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