Journal Article


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

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.

Attached files

Authors

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

Oxford Brookes departments

Faculty of Health and Life Sciences\Department of Biological and Medical Sciences

Dates

Year of publication: 2017
Date of RADAR deposit: 2017-03-14



http://www.nature.com/authors/policies/license.html - For terms of reuse of archived manuscripts see the licence link


Related resources

This RADAR resource is the Accepted Manuscript of De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Details

  • Owner: Rosa Teira Paz
  • Collection: Outputs
  • Version: 1 (show all)
  • Status: Live