Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia
Summary: Pathogenic variants in KIAA0586/TALPID3 are associated with the ciliopathy Joubert syndrome (JS). We report individuals with KIAA0586/TALPID3 variants affected by primary and motile cilia defects leading to JS and chronic destructive airway disease. DNA variants were detected in three famil...
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028979 |
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| author | Jacqueline E. Taudien Diana Bracht Heike Olbrich Sebastian Swirski Fulvio D’Abrusco Bert Van der Zwaag Maike Möller Thomas Lücke Norbert Teig Ulrika Lindberg Kai Wohlgemuth Julia Wallmeier Anja Blanque Christos Gatsogiannis Sebastian George Christoph Jüschke Marta Owczarek-Lipska Dorothee Veer Hester Y. Kroes Enza Maria Valente G. Christoph Korenke Heymut Omran John Neidhardt |
| author_facet | Jacqueline E. Taudien Diana Bracht Heike Olbrich Sebastian Swirski Fulvio D’Abrusco Bert Van der Zwaag Maike Möller Thomas Lücke Norbert Teig Ulrika Lindberg Kai Wohlgemuth Julia Wallmeier Anja Blanque Christos Gatsogiannis Sebastian George Christoph Jüschke Marta Owczarek-Lipska Dorothee Veer Hester Y. Kroes Enza Maria Valente G. Christoph Korenke Heymut Omran John Neidhardt |
| author_sort | Jacqueline E. Taudien |
| collection | DOAJ |
| description | Summary: Pathogenic variants in KIAA0586/TALPID3 are associated with the ciliopathy Joubert syndrome (JS). We report individuals with KIAA0586/TALPID3 variants affected by primary and motile cilia defects leading to JS and chronic destructive airway disease. DNA variants were detected in three families by sequencing. In two unrelated families, a deep-intronic variant (KIAA0586/TALPID3:c.3990 + 3186G>A) activated a cryptic exon. We performed histological and functional analyses in native and air-liquid interface (ALI) cultured respiratory cells. Primary cilia lengths were measured in patient-derived fibroblasts. Our data associate KIAA0586/TALPID3 variants with a syndrome combining JS and chronic destructive airway disease, reduced number of motile cilia, disorganized basal body location, and ciliary clearance malfunction. Additionally, patient-derived cell lines showed primary cilia defects. Disease causing KIAA0586/TALPID3 variants, including a deep-intronic sequence variant, were associated with primary and motile cilia defects in JS patients. The combination of JS and respiratory symptoms should be considered indicative for KIAA0586/TALPID3 sequence alterations. |
| format | Article |
| id | doaj-art-7a7a4c3e3422406b806dee39a3c4b48f |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-7a7a4c3e3422406b806dee39a3c4b48f2025-01-16T04:29:09ZengElsevieriScience2589-00422025-02-01282111670Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile ciliaJacqueline E. Taudien0Diana Bracht1Heike Olbrich2Sebastian Swirski3Fulvio D’Abrusco4Bert Van der Zwaag5Maike Möller6Thomas Lücke7Norbert Teig8Ulrika Lindberg9Kai Wohlgemuth10Julia Wallmeier11Anja Blanque12Christos Gatsogiannis13Sebastian George14Christoph Jüschke15Marta Owczarek-Lipska16Dorothee Veer17Hester Y. Kroes18Enza Maria Valente19G. Christoph Korenke20Heymut Omran21John Neidhardt22Human Genetics, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, 26129 Oldenburg, GermanyDepartment of General Paediatrics, University Hospital Muenster, 48149 Muenster, GermanyDepartment of General Paediatrics, University Hospital Muenster, 48149 Muenster, GermanyHuman Genetics, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, 26129 Oldenburg, GermanyNeurogenetics Research Centre, IRCCS Mondino Foundation, 27100 Pavia, ItalyDivision Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center of Utrecht, 3584 CX Utrecht, the NetherlandsHuman Genetics, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, 26129 Oldenburg, GermanyDepartment of Neuropaediatrics and Social Paediatrics, University Children’s Hospital, Ruhr-University Bochum, 44791 Bochum, GermanyDepartment of Neonatalogy, University Children’s Hospital, Ruhr-University Bochum, 44791 Bochum, GermanyLund University, Skåne University Hospital, Department of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund, SwedenDepartment of General Paediatrics, University Hospital Muenster, 48149 Muenster, GermanyDepartment of General Paediatrics, University Hospital Muenster, 48149 Muenster, GermanyInstitute for Medical Physics and Biophysics and Center for Soft Nanoscience (SoN), Westfälische Wilhelms University Münster, 48149 Münster, GermanyInstitute for Medical Physics and Biophysics and Center for Soft Nanoscience (SoN), Westfälische Wilhelms University Münster, 48149 Münster, GermanyDepartment of General Paediatrics, University Hospital Muenster, 48149 Muenster, GermanyHuman Genetics, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, 26129 Oldenburg, GermanyHuman Genetics, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, 26129 Oldenburg, Germany; Research Center Neurosensory Science, University of Oldenburg, 26129 Oldenburg, GermanySocial-pediatric Outpatient and Therapy Center, Hospital Ludmillenstift, 49716 Meppen, GermanyDivision Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center of Utrecht, 3584 CX Utrecht, the NetherlandsNeurogenetics Research Centre, IRCCS Mondino Foundation, 27100 Pavia, Italy; Department of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyUniversity Children’s Hospital Oldenburg, Department of Neuropaediatric and Metabolic Diseases, 26133 Oldenburg, GermanyDepartment of General Paediatrics, University Hospital Muenster, 48149 Muenster, GermanyHuman Genetics, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, 26129 Oldenburg, Germany; Research Center Neurosensory Science, University of Oldenburg, 26129 Oldenburg, Germany; Corresponding authorSummary: Pathogenic variants in KIAA0586/TALPID3 are associated with the ciliopathy Joubert syndrome (JS). We report individuals with KIAA0586/TALPID3 variants affected by primary and motile cilia defects leading to JS and chronic destructive airway disease. DNA variants were detected in three families by sequencing. In two unrelated families, a deep-intronic variant (KIAA0586/TALPID3:c.3990 + 3186G>A) activated a cryptic exon. We performed histological and functional analyses in native and air-liquid interface (ALI) cultured respiratory cells. Primary cilia lengths were measured in patient-derived fibroblasts. Our data associate KIAA0586/TALPID3 variants with a syndrome combining JS and chronic destructive airway disease, reduced number of motile cilia, disorganized basal body location, and ciliary clearance malfunction. Additionally, patient-derived cell lines showed primary cilia defects. Disease causing KIAA0586/TALPID3 variants, including a deep-intronic sequence variant, were associated with primary and motile cilia defects in JS patients. The combination of JS and respiratory symptoms should be considered indicative for KIAA0586/TALPID3 sequence alterations.http://www.sciencedirect.com/science/article/pii/S2589004224028979Cell biologyCellular physiologyHuman GeneticsIntegrative aspects of cell biology |
| spellingShingle | Jacqueline E. Taudien Diana Bracht Heike Olbrich Sebastian Swirski Fulvio D’Abrusco Bert Van der Zwaag Maike Möller Thomas Lücke Norbert Teig Ulrika Lindberg Kai Wohlgemuth Julia Wallmeier Anja Blanque Christos Gatsogiannis Sebastian George Christoph Jüschke Marta Owczarek-Lipska Dorothee Veer Hester Y. Kroes Enza Maria Valente G. Christoph Korenke Heymut Omran John Neidhardt Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia iScience Cell biology Cellular physiology Human Genetics Integrative aspects of cell biology |
| title | Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia |
| title_full | Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia |
| title_fullStr | Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia |
| title_full_unstemmed | Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia |
| title_short | Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia |
| title_sort | pathogenic kiaa0586 talpid3 variants are associated with defects in primary and motile cilia |
| topic | Cell biology Cellular physiology Human Genetics Integrative aspects of cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224028979 |
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