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Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia

Taudien, Jacqueline E. ; Bracht, Diana ; Olbrich, Heike ; Swirski, Sebastian ; D'Abrusco, Fulvio ; Van der Zwaag, Bert ; Möller, Maike ; Lücke, Thomas ; Teig, Norbert and Lindberg, Ulrika LU , et al. (2025) In iScience 28(2).
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Cell biology, Cellular physiology, Human Genetics, Integrative aspects of cell biology
in
iScience
volume
28
issue
2
article number
111670
publisher
Elsevier
external identifiers
  • scopus:85214788404
  • pmid:39898050
ISSN
2589-0042
DOI
10.1016/j.isci.2024.111670
language
English
LU publication?
yes
id
1e7b2b8a-b017-466f-ace2-ac6fdd19ec63
date added to LUP
2025-03-12 15:36:41
date last changed
2025-07-17 02:44:04
@article{1e7b2b8a-b017-466f-ace2-ac6fdd19ec63,
  abstract     = {{<p>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&gt;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.</p>}},
  author       = {{Taudien, Jacqueline E. and Bracht, Diana and Olbrich, Heike and Swirski, Sebastian and D'Abrusco, Fulvio and Van der Zwaag, Bert and Möller, Maike and Lücke, Thomas and Teig, Norbert and Lindberg, Ulrika and Wohlgemuth, Kai and Wallmeier, Julia and Blanque, Anja and Gatsogiannis, Christos and George, Sebastian and Jüschke, Christoph and Owczarek-Lipska, Marta and Veer, Dorothee and Kroes, Hester Y. and Valente, Enza Maria and Korenke, G. Christoph and Omran, Heymut and Neidhardt, John}},
  issn         = {{2589-0042}},
  keywords     = {{Cell biology; Cellular physiology; Human Genetics; Integrative aspects of cell biology}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2024.111670}},
  doi          = {{10.1016/j.isci.2024.111670}},
  volume       = {{28}},
  year         = {{2025}},
}