The Epigenetic Regulator SMCHD1 in Development and Disease

Trends Genet. 2017 Apr;33(4):233-243. doi: 10.1016/j.tig.2017.01.007. Epub 2017 Feb 20.


It has very recently become clear that the epigenetic modifier SMCHD1 has a role in two distinct disorders: facioscapulohumoral muscular dystrophy (FSHD) and Bosma arhinia and micropthalmia (BAMS). In the former there are heterozygous loss-of-function mutations, while both gain- and loss-of-function mutations have been proposed to underlie the latter. These findings have led to much interest in SMCHD1 and how it works at the molecular level. We summarise here current understanding of the mechanism of action of SMCHD1, its role in these diseases, and what has been learnt from study of mouse models null for Smchd1 in the decade since the discovery of SMCHD1.

Keywords: Bosma arhinia and micropthalmia syndrome; SMCHD1; epigenetic silencing; facioscapulohumoral muscular dystrophy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Choanal Atresia / genetics*
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA Methylation / genetics
  • Epigenesis, Genetic*
  • Heterozygote
  • Humans
  • Mice
  • Microphthalmos / genetics*
  • Muscular Dystrophy, Facioscapulohumeral / genetics*
  • Mutation
  • Nose / abnormalities*


  • Chromosomal Proteins, Non-Histone
  • SMCHD1 protein, human

Supplementary concepts

  • Arhinia, choanal atresia, and microphthalmia