TMEM107 Is a Critical Regulator of Ciliary Protein Composition and Is Mutated in Orofaciodigital Syndrome

Hum Mutat. 2016 Feb;37(2):155-9. doi: 10.1002/humu.22925. Epub 2015 Nov 23.

Abstract

The proximate causes of multiple human genetic syndromes (ciliopathies) are disruptions in the formation or function of the cilium, an organelle required for a multitude of developmental processes. We previously identified Tmem107 as a critical regulator of cilia formation and embryonic organ development in the mouse. Here, we describe a patient with a mutation in TMEM107 that developed atypical Orofaciodigital syndrome (OFD), and show that the OFD patient shares several morphological features with the Tmem107 mutant mouse including polydactyly and reduced numbers of ciliated cells. We show that TMEM107 appears to function within cilia to regulate protein content, as key ciliary proteins do not localize normally in cilia derived from the Tmem107 mouse mutant and the human patient. These data indicate that TMEM107 plays a key, conserved role in regulating ciliary protein composition, and is a novel candidate for ciliopathies of unknown etiology.

Keywords: Orofaciodigital syndrome; TMEM107; cilia; cilia protein composition; ciliopathy.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Child, Preschool
  • Cilia / genetics*
  • Cilia / pathology
  • Exome
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Orofaciodigital Syndromes / diagnosis
  • Orofaciodigital Syndromes / genetics*
  • Orofaciodigital Syndromes / mortality
  • Primary Cell Culture
  • Sequence Alignment

Substances

  • Membrane Proteins
  • TMEM107 protein, human
  • Tmem107 protein, mouse