title: OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome.
abstract: Oral-facial-digital (OFD) syndromes are rare heterogeneous disorders characterized by the association of abnormalities of the face, the oral cavity and the extremities, some due to mutations in proteins of the transition zone of the primary cilia or the closely associated distal end of centrioles. These two structures are essential for the formation of functional cilia, and for signaling events during development. We report here causal compound heterozygous mutations of KIAA0753/OFIP in a patient with an OFD VI syndrome. We show that the KIAA0753/OFIP protein, whose sequence is conserved in ciliated species, associates with centrosome/centriole and pericentriolar satellites in human cells and forms a complex with FOR20 and OFD1. The decreased expression of any component of this ternary complex in RPE1 cells causes a defective recruitment onto centrosomes and satellites. The OFD KIAA0753/OFIP mutant loses its capacity to interact with FOR20 and OFD1, which may be the molecular basis of the defect. We also show that KIAA0753/OFIP has microtubule-stabilizing activity. OFD1 and FOR20 are known to regulate the integrity of the centriole distal end, confirming that this structural element is a target of importance for pathogenic mutations in ciliopathies.
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, Institut Paoli-Calmettes and CNRS U7258, F-13009 Marseille, France, Aix-Marseille Université, F-13007 Marseille, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Chevrier
authors.affiliation: Equipe d'Accueil 4271, Génétique des Anomalies du Développement, Université Fédérale Bourgogne - Franche Comté, F-21079 Dijon, France, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD).
authors.forename: Ange-Line
authors.initials: AL
authors.lastname: Bruel
authors.affiliation: Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Teunis J P
authors.initials: TJ
authors.lastname: Van Dam
authors.affiliation: Telethon Institute of Genetics and Medicine, Naples, Italy, Medical Genetics, Department of Medical Translational Sciences, University of Napoli Federico II, Naples, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
authors.affiliation: All Children Hospital, Saint Petersburg, FL, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lo Scalzo
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, Institut Paoli-Calmettes and CNRS U7258, F-13009 Marseille, France, Aix-Marseille Université, F-13007 Marseille, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Lembo
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, Institut Paoli-Calmettes and CNRS U7258, F-13009 Marseille, France, Aix-Marseille Université, F-13007 Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Audebert
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, Institut Paoli-Calmettes and CNRS U7258, F-13009 Marseille, France, Aix-Marseille Université, F-13007 Marseille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Baudelet
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, Institut Paoli-Calmettes and CNRS U7258, F-13009 Marseille, France, Aix-Marseille Université, F-13007 Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Isnardon
authors.affiliation: Aix-Marseille Université, F-13007 Marseille, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Bole
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, Institut Paoli-Calmettes and CNRS U7258, F-13009 Marseille, France, Aix-Marseille Université, F-13007 Marseille, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Borg
authors.affiliation: Equipe d'Accueil 4271, Génétique des Anomalies du Développement, Université Fédérale Bourgogne - Franche Comté, F-21079 Dijon, France, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD).
authors.forename: Paul
authors.initials: P
authors.lastname: Kuentz
authors.affiliation: Equipe d'Accueil 4271, Génétique des Anomalies du Développement, Université Fédérale Bourgogne - Franche Comté, F-21079 Dijon, France, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est.
authors.forename: Julien
authors.initials: J
authors.lastname: Thevenon
authors.affiliation: Centre de Référence des Malformations et Maladies Congénitales du Cervelet and Service de Génétique, Hôpital Armand Trousseau, AP-HP, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Burglen
authors.affiliation: Equipe d'Accueil 4271, Génétique des Anomalies du Développement, Université Fédérale Bourgogne - Franche Comté, F-21079 Dijon, France, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: Equipe d'Accueil 4271, Génétique des Anomalies du Développement, Université Fédérale Bourgogne - Franche Comté, F-21079 Dijon, France, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, Centre Hospitalier Universitaire Dijon, Dijon F-21079, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Rivière
authors.affiliation: Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Huynen
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, Institut Paoli-Calmettes and CNRS U7258, F-13009 Marseille, France, Aix-Marseille Université, F-13007 Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM UMR1068, Institut Paoli-Calmettes and CNRS U7258, F-13009 Marseille, France, Aix-Marseille Université, F-13007 Marseille, France, christel.thauvin@chu-dijon.fr olivier.rosnet@inserm.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rosnet
authors.affiliation: Equipe d'Accueil 4271, Génétique des Anomalies du Développement, Université Fédérale Bourgogne - Franche Comté, F-21079 Dijon, France, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Interrégion Est, christel.thauvin@chu-dijon.fr olivier.rosnet@inserm.fr.
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D002923:Cilia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017124:Conserved Sequence; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009958:Orofaciodigital Syndromes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: C553664:CEP20 protein, human; C000612074:KIAA0753 protein, human; D008869:Microtubule-Associated Proteins; C115130:OFD1 protein, human; D011506:Proteins