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


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Gordon C. T., Xue S., Yigit G., Filali H., Chen K., Rosins N., ...Daha Fazla

NATURE GENETICS, cilt.49, sa.2, ss.249-255, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 49 Sayı: 2
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1038/ng.3765
  • Dergi Adı: NATURE GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.249-255
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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.