ArticleAmerican journal of human genetics2020
TTC12 Loss-of-Function Mutations Cause Primary Ciliary Dyskinesia and Unveil Distinct Dynein Assembly Mechanisms in Motile Cilia Versus Flagella.
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Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 73 citations in OpenAlex.
- Comparative genomic analysis of pigs differing in survival following African swine fever virus infection.Veterinary research communications · 2026Article
- A Rare Case of Co-occurring Fanconi Anemia and Primary Ciliary DyskinesiaTurkish journal of haematology : official journal of Turkish Society of Haematology · 2026Article
- Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility.Asian journal of andrology · 2025Article
- The RaDiCo information system for rare disease cohorts.Orphanet journal of rare diseases · 2025Article
- IQUB mutation induces radial spoke 1 deficiency causing asthenozoospermia with normal sperm morphology in humans and mice.Cell communication and signaling : CCS · 2025Article
- A novel homozygous missense TTC12 variant identified in an infertile Pakistani man with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia.Molecular genetics and genomics : MGG · 2024Article
- Primary Ciliary Dyskinesia: A Clinical Review.Cells · 2024Review
- Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation.Science China. Life sciences · 2024Article
- Lack of CFAP54 causes primary ciliary dyskinesia in a mouse model and human patients.Frontiers of medicine · 2023Article
- BBOF1 is required for sperm motility and male fertility by stabilizing the flagellar axoneme in mice.Cellular and molecular life sciences : CMLS · 2023Article
- The impact of primary ciliary dyskinesia on female and male fertility: a narrative review.Human reproduction update · 2023Review
- Review
- Novel homozygous variants inFrontiers in cell and developmental biology · 2023Article
- Biallelic mutations of TTC12 and TTC21B were identified in Chinese patients with multisystem ciliopathy syndromes.Human genomics · 2022Article
- The dynamics of protein localisation to restricted zones within Drosophila mechanosensory cilia.Scientific reports · 2022Article
- The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization.Biomolecules · 2022Review
- Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening.Cell death & disease · 2022Article
- Perspectives for Primary Ciliary Dyskinesia.International journal of molecular sciences · 2022Article
- PCD Genes-From Patients to Model Organisms and Back to Humans.International journal of molecular sciences · 2022Review
- Review
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Authors and funding
33 authors at 12 institutions in 1 country.
Lucie ThomasSorbonne Université, Institut National de la Santé et de la Recherche Médicale, U933, Hôpital Armand-Trousseau, Paris 75012, France.
Khaled BouhoucheInstitute for Integrative Biology of the Cell (I2BC), Centre à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
Marjorie WhitfieldInstitut Cochin, Institut National de la Santé et de la Recherche Médicale, U1016), Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Paris 75014, France.
Guillaume ThouveninUnité Fonctionnelle d'Exploration Fonctionnelle Respiratoire - Somnologie, Service de Physiologie et Explorations Fonctionnelles, Centre National de Référence des Maladies Respiratoires Rares, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France; Centre de Recherche Saint-Antoine, Sorbonne Universités, Paris 75012, France.
Andre CosteHôpital Henri Mondor et Centre Hospitalier Intercommunal de Créteil, Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Assistance Publique-Hôpitaux de Paris, Créteil 94010, France; Faculté de Médecine, Université Paris-Est, Institut National de la Santé et de la Recherche Médicale, U955), Centre National de la Recherche Scientifique ERL7240, Hôpital Henri Mondor, Créteil 94010, France.
Bruno LouisFaculté de Médecine, Université Paris-Est, Institut National de la Santé et de la Recherche Médicale, U955), Centre National de la Recherche Scientifique ERL7240, Hôpital Henri Mondor, Créteil 94010, France.
Claire SzymanskiService d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Hôpital Huriez, Centre Hospitalier Universitaire Lille, Lille 59000, France.
Emilie BequignonHôpital Henri Mondor et Centre Hospitalier Intercommunal de Créteil, Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Assistance Publique-Hôpitaux de Paris, Créteil 94010, France; Faculté de Médecine, Université Paris-Est, Institut National de la Santé et de la Recherche Médicale, U955), Centre National de la Recherche Scientifique ERL7240, Hôpital Henri Mondor, Créteil 94010, France.
Jean-François PaponFaculté de Médecine, Université Paris-Est, Institut National de la Santé et de la Recherche Médicale, U955), Centre National de la Recherche Scientifique ERL7240, Hôpital Henri Mondor, Créteil 94010, France; Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre 94275, France.
Manon CastelliInstitute for Integrative Biology of the Cell (I2BC), Centre à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
Michel LemulloisInstitute for Integrative Biology of the Cell (I2BC), Centre à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
Xavier DhalluinServices de Pneumologie et Oncologie Thoracique et d'endoscopie respiratoire, Hôpital Calmette, Centre Hospitalier Universitaire Lille, Lille 59000, France.
Valérie Drouin-GarraudService de Génétique Médicale, Hôpital Charles Nicolle, Centre Hospitalier Universitaire-Hôpitaux de Rouen, Rouen 76000, France.
Guy MontantinDépartement de Génétique Médicale, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France.
Sylvie TissierDépartement de Génétique Médicale, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France.
Philippe DuquesnoySorbonne Université, Institut National de la Santé et de la Recherche Médicale, U933, Hôpital Armand-Trousseau, Paris 75012, France.
Bruno CopinDépartement de Génétique Médicale, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France.
Florence DastotDépartement de Génétique Médicale, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France.
Sandrine CouvetSorbonne Université, Institut National de la Santé et de la Recherche Médicale, U933, Hôpital Armand-Trousseau, Paris 75012, France.
Anne-Laure BarbotinInstitut de Biologie de la Reproduction-Spermiologie-Cecos, Hôpital Jeanne de Flandre, Centre Hospitalier Universitaire Lille, Lille 59000, France; EA4308: Gametogenesis and Gamete Quality, Université de Lille, Lille 59000, France.
Catherine FauconCentre Hospitalier Intercommunal de Créteil, Laboratoire de Microscopie Électronique, Service d'Anatomopathologie, Créteil 94010, France.
Isabelle HonoreService de Pneumologie et Oncologie Thoracique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris 75014, France.
Bernard MaitreService de Pneumologie, Hôpital Henri Mondor et Centre Hospitalier Intercommunal de Créteil, Assistance Publique-Hôpitaux de Paris, Créteil 94010, France.
Nicole BeydonUnité Fonctionnelle d'Exploration Fonctionnelle Respiratoire - Somnologie, Service de Physiologie et Explorations Fonctionnelles, Centre National de Référence des Maladies Respiratoires Rares, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France.
Aline TamaletUnité Fonctionnelle d'Exploration Fonctionnelle Respiratoire - Somnologie, Service de Physiologie et Explorations Fonctionnelles, Centre National de Référence des Maladies Respiratoires Rares, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France.
Nathalie RivesDepartment of Reproductive Biology-Centre d'Étude et de Conservation du Sperme, Normandie Université, UNIROUEN, EA 4308 "Gametogenesis and Gamete Quality," Rouen University Hospital, Rouen 76000, France.
France KollInstitute for Integrative Biology of the Cell (I2BC), Centre à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
Estelle EscudierSorbonne Université, Institut National de la Santé et de la Recherche Médicale, U933, Hôpital Armand-Trousseau, Paris 75012, France; Département de Génétique Médicale, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France.
Anne-Marie TassinInstitute for Integrative Biology of the Cell (I2BC), Centre à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
Aminata TouréInstitut Cochin, Institut National de la Santé et de la Recherche Médicale, U1016), Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Paris 75014, France. Electronic address: aminata.toure@inserm.fr.
Valérie MitchellInstitut de Biologie de la Reproduction-Spermiologie-Cecos, Hôpital Jeanne de Flandre, Centre Hospitalier Universitaire Lille, Lille 59000, France; EA4308: Gametogenesis and Gamete Quality, Université de Lille, Lille 59000, France.
Serge AmselemSorbonne Université, Institut National de la Santé et de la Recherche Médicale, U933, Hôpital Armand-Trousseau, Paris 75012, France; Département de Génétique Médicale, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France. Electronic address: serge.amselem@inserm.fr.
Marie LegendreSorbonne Université, Institut National de la Santé et de la Recherche Médicale, U933, Hôpital Armand-Trousseau, Paris 75012, France; Département de Génétique Médicale, Hôpital Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, Paris 75012, France.
Inserm · FRSorbonne Université · FRUniversité Paris-Sud · FRCentre Hospitalier Universitaire de Lille · FRUniversité Paris Cité · FRCentre Hospitalier Universitaire Henri-Mondor · FRHôpital Albert Calmette · FRHôpital Charles-Nicolle · FRHôpital Cochin · FRHôpital Intercommunal de Créteil · FRLaboratoire de Biomécanique et Mécanique des Chocs · FRNormandie Université · FR
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs and IDAs). Defects in ODAs and IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. PCD mutations in assembly factors have been shown to cause a combined ODA-IDA defect, affecting both cilia and flagella. We identified four loss-of-function mutations in TTC12, which encodes a cytoplasmic protein, in four independent families in which affected individuals displayed a peculiar PCD phenotype characterized by the absence of ODAs and IDAs in sperm flagella, contrasting with the absence of only IDAs in respiratory cilia. Analyses of both primary cells from individuals carrying TTC12 mutations and human differentiated airway cells invalidated for TTC12 by a CRISPR-Cas9 approach revealed an IDA defect restricted to a subset of single-headed IDAs that are different in flagella and cilia, whereas TTC12 depletion in the ciliate Paramecium tetraurelia recapitulated the sperm phenotype. Overall, our study, which identifies TTC12 as a gene involved in PCD, unveils distinct dynein assembly mechanisms in human motile cilia versus flagella.
Indexed as
MutationAdultAxonemeChildCiliaCiliary Motility DisordersDyneinsFemaleFlagellaHomozygoteHumansInfertility, MaleMaleMiddle AgedPedigreePhenotypeDyneinsProteinsTTC12 protein, humanciliaCRISPR-Cas9dynein arm assemblyprimary ciliary dyskinesiasperm flagellaTTC12
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