2. Academic Validation
  3. TMEM107 Is a Critical Regulator of Ciliary Protein Composition and Is Mutated in Orofaciodigital Syndrome

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.
Natalia A Shylo 1,  Kasey J Christopher 1,  Alejandro Iglesias 2,  Aaron Daluiski 3,  Scott D Weatherbee 1
Affiliations

Affiliations

  • 1 Department of Genetics, Yale University, School of Medicine, P.O. Box 208005, SHM I-142D, 333 Cedar Street, New Haven, CT, 06520.
  • 2 Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York.
  • 3 Department of Hand and Upper Extremity Surgery, Hospital for Special Surgery, New York, New York.
PMID: 26518474 DOI: 10.1002/humu.22925
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.

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