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 ValenteG. 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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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",

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 - http://www.scopus.com/inward/record.url?scp=85214788404&partnerID=8YFLogxK

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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