Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia
Pathogenic variants in <i>KIAA0586/TALPID3</i> are associated with the ciliopathy Joubert syndrome (JS). We report individuals with <i>KIAA0586/TALPID3</i> 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 (<i>KIAA0586/TALPID3</i>: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 <i>KIAA0586/TALPID3</i> 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 <i>KIAA0586/TALPID3</i> 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 <i>KIAA0586/TALPID3</i> sequence alterations.
Authors
- Heymut Omran (ORCID: https://orcid.org/0000-0003-0282-6765)
- Uno Lindberg
- Kai Wohlgemuth (ORCID: https://orcid.org/0000-0003-4092-0664)
- Sebastian Swirski (ORCID: https://orcid.org/0000-0002-6793-3070)
- Christos Gatsogiannis (ORCID: https://orcid.org/0000-0002-4922-4545)
- Fulvio D’Abrusco (ORCID: https://orcid.org/0000-0003-2470-665X)
- Sebastian George (ORCID: https://orcid.org/0000-0002-3768-734X)
- Heike Olbrich (ORCID: https://orcid.org/0000-0003-4355-353X)
- Julia Wallmeier (ORCID: https://orcid.org/0000-0002-3958-9065)
- Morten Hylander Møller (ORCID: https://orcid.org/0000-0002-6378-9673)
- Marta Owczarek‐Lipska (ORCID: https://orcid.org/0000-0001-6667-4452)
- John Neidhardt (ORCID: https://orcid.org/0000-0002-9205-8394)
- Enza Maria Valente (ORCID: https://orcid.org/0000-0002-0600-6820)
- Christoph Jüschke (ORCID: https://orcid.org/0000-0001-5842-4824)
- Diana Bracht (ORCID: https://orcid.org/0000-0002-2151-038X)
- Norbert Teig
- Bert van der Zwaag
- G. Christoph Korenke
- Hester Y. Kroes
- Thomas Lücke (ORCID: https://orcid.org/0000-0001-6875-6582)
- Jacqueline E Taudien
- Anja Blanque
- Dorothee Veer
Institutions
- Carl von Ossietzky Universität Oldenburg (DE)
- Lund University (SE)
- Utrecht University (NL)
- University of Münster (DE)
- University of Pavia (IT)
- University Hospitals of the Ruhr-University of Bochum (DE)
- University Medical Center Utrecht (NL)
- Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IT)
- University Hospital Münster (DE)
- Klinikum Oldenburg (DE)
- Kanti Children's Hospital (NP)
- Skåne University Hospital (SE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- iScience
- Published
- 2024-12-21
- DOI
- https://doi.org/10.1016/j.isci.2024.111670
- Citations
- 3
- Primary Topic
- Genetic and Kidney Cyst Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.65
Funders
- Carl von Ossietzky Universität Oldenburg