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Nat Genet 2017 Feb 01;492:249-255. doi: 10.1038/ng.3765.
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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 , Altmüller J , Dion C , Thiele H , Gurzau AD , Nürnberg P , Meschede D , Mühlbauer 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 , Nitschké P , Ragge N , Lévy N , Tunçbilek 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 .

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.

PubMed ID: 28067911
Article link: Nat Genet
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: rax six1 smchd1 twist1

Phenotypes: Xla Wt + smchd1 (Fig 3. f)

Article Images: [+] show captions