title: TMEM107 Is a Critical Regulator of Ciliary Protein Composition and Is Mutated in Orofaciodigital Syndrome.
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.
authors.affiliation: Department of Genetics, Yale University, School of Medicine, P.O. Box 208005, SHM I-142D, 333 Cedar Street, New Haven, CT, 06520.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Shylo
authors.affiliation: Department of Genetics, Yale University, School of Medicine, P.O. Box 208005, SHM I-142D, 333 Cedar Street, New Haven, CT, 06520.
authors.forename: Kasey J
authors.initials: KJ
authors.lastname: Christopher
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Department of Hand and Upper Extremity Surgery, Hospital for Special Surgery, New York, New York.
authors.forename: Aaron
authors.initials: A
authors.lastname: Daluiski
authors.affiliation: Department of Genetics, Yale University, School of Medicine, P.O. Box 208005, SHM I-142D, 333 Cedar Street, New Haven, CT, 06520.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Weatherbee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D002923:Cilia / Q000235:genetics* / Q000473:pathology; D059472:Exome; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009958:Orofaciodigital Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D061251:Primary Cell Culture; D016415:Sequence Alignment
chemical_list: D008565:Membrane Proteins; C000607975:TMEM107 protein, human; C575829:Tmem107 protein, mouse
keywords: Orofaciodigital syndrome; TMEM107; cilia; cilia protein composition; ciliopathy