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

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

doi:10.1016/j.isci.2024.111670

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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 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.

Original language	English
Article number	111670
Journal	iScience
Volume	28
Issue number	2
DOIs	https://doi.org/10.1016/j.isci.2024.111670
Publication status	Published - 21 Feb 2025

Keywords

Cell biology
Cellular physiology
Human Genetics
Integrative aspects of cell biology

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10.1016/j.isci.2024.111670Licence: CC BY-NC

PIIS2589004224028979Final published version, 5.4 MBLicence: CC BY-NC

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Taudien, J. E., Bracht, D., Olbrich, H., Swirski, S., D'Abrusco, F., Van der Zwaag, B., Möller, M., Lücke, T., Teig, N., Lindberg, U., Wohlgemuth, K., Wallmeier, J., Blanque, A., Gatsogiannis, C., George, S., Jüschke, C., Owczarek-Lipska, M., Veer, D., Kroes, H. Y., ... Neidhardt, J. (2025). Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia. iScience, 28(2), Article 111670. https://doi.org/10.1016/j.isci.2024.111670

@article{43288c2437c14f60b00eb5f6b9f34ed7,

title = "Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia",

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 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.",

keywords = "Cell biology, Cellular physiology, Human Genetics, Integrative aspects of cell biology",

author = "Taudien, \{Jacqueline E.\} and Diana Bracht and Heike Olbrich and Sebastian Swirski and Fulvio D'Abrusco and \{Van der Zwaag\}, Bert and Maike M{\"o}ller and Thomas L{\"u}cke and Norbert Teig and Ulrika Lindberg and Kai Wohlgemuth and Julia Wallmeier and Anja Blanque and Christos Gatsogiannis and Sebastian George and Christoph J{\"u}schke and Marta Owczarek-Lipska and Dorothee Veer and Kroes, \{Hester Y.\} and Valente, \{Enza Maria\} and Korenke, \{G. Christoph\} and Heymut Omran and John Neidhardt",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2025",

month = feb,

day = "21",

doi = "10.1016/j.isci.2024.111670",

language = "English",

volume = "28",

journal = "iScience",

publisher = "Elsevier",

number = "2",

}

Taudien, JE, Bracht, D, Olbrich, H, Swirski, S, D'Abrusco, F, Van der Zwaag, B, Möller, M, Lücke, T, Teig, N, Lindberg, U, Wohlgemuth, K, Wallmeier, J, Blanque, A, Gatsogiannis, C, George, S, Jüschke, C, Owczarek-Lipska, M, Veer, D, Kroes, HY, Valente, EM, Korenke, GC, Omran, H & Neidhardt, J 2025, 'Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia', iScience, vol. 28, no. 2, 111670. https://doi.org/10.1016/j.isci.2024.111670

TY - JOUR

T1 - Pathogenic KIAA0586/TALPID3 variants are associated with defects in primary and motile cilia

AU - Taudien, Jacqueline E.

AU - Bracht, Diana

AU - Olbrich, Heike

AU - Swirski, Sebastian

AU - D'Abrusco, Fulvio

AU - Van der Zwaag, Bert

AU - Möller, Maike

AU - Lücke, Thomas

AU - Teig, Norbert

AU - Lindberg, Ulrika

AU - Wohlgemuth, Kai

AU - Wallmeier, Julia

AU - Blanque, Anja

AU - Gatsogiannis, Christos

AU - George, Sebastian

AU - Jüschke, Christoph

AU - Owczarek-Lipska, Marta

AU - Veer, Dorothee

AU - Kroes, Hester Y.

AU - Valente, Enza Maria

AU - Korenke, G. Christoph

AU - Omran, Heymut

AU - Neidhardt, John

PY - 2025/2/21

Y1 - 2025/2/21

N2 - 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.

AB - 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.

KW - Cell biology

KW - Cellular physiology

KW - Human Genetics

KW - Integrative aspects of cell biology

UR - https://www.scopus.com/pages/publications/85214788404

U2 - 10.1016/j.isci.2024.111670

DO - 10.1016/j.isci.2024.111670

M3 - Article

AN - SCOPUS:85214788404

VL - 28

JO - iScience

JF - iScience

IS - 2

M1 - 111670

ER -

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

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