Truncating Variants in KIF5C Cause a Milder Disorder Distinct From KIF5C-Associated Cortical Dysplasia

Kulosik L, Schanze I, Zacher P, Al-Awam BS, Srinivasan VM, Gowda VK, Krey I, Fuchs A, Goldenberg A, Saugier-Veber P, Hashemi-Gorji F, Yassaee VR, Zenker M, Sticht H, Jamra RA, Neuser S (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Pediatric Neurology Elsevier

Book Volume: 179

Pages Range: 37-44

DOI: 10.1016/j.pediatrneurol.2026.03.004

Abstract

Background: Distinct, recurrent missense variants in KIF5C have previously been described in a small number of patients with cortical dysplasia and severe intellectual disability. We aimed to further characterize the phenotype associated with KIF5C variants, including truncating variants. Methods: We analyzed ten newly identified individuals with disease-associated KIF5C variants and compared them to previously reported cases. The variant spectrum was evaluated in a multicenter case series, and a cross-sectional analysis of the phenotypic range was performed. Molecular modeling was used to identify variant clusters and to provide insights into their potential functional effects. Results: In our cohort of 19 individuals (ten newly and nine previously reported), we identified eight distinct variants: three truncating, four missense, and one in-frame deletion. Individuals with missense variants consistently exhibited severe developmental delay, absence of speech, seizures, and malformations of cortical development. In contrast, individuals with truncating variants showed milder developmental delay, less severe speech impairment, and no malformations of cortical development. Conclusions: Our findings suggest a genotype-phenotype correlation in KIF5C, with truncating variants associated with a milder phenotype compared to missense variants.

Authors with CRIS profile

Heinrich Sticht Professur für Bioinformatik

Involved external institutions

Universität Leipzig DE Germany (DE) Universitätsklinikum Magdeburg A.ö.R. DE Germany (DE) Kleinwachau - Sächsisches Epilepsiezentrum Radeberg gGmbH DE Germany (DE) King Fahd Hospital of the University / شاہ فہد یونیورسٹی ہسپتال SA Saudi Arabia (SA) Indira Gandhi Institute of Child Health IN India (IN) Evangelisches Krankenhaus Königin Elisabeth Herzberge DE Germany (DE) University of Rouen / Université de Rouen FR France (FR) Shahid Beheshti University of Medical Sciences IR Iran, Islamic Republic of (IR)

How to cite

APA:

Kulosik, L., Schanze, I., Zacher, P., Al-Awam, B.S., Srinivasan, V.M., Gowda, V.K.,... Neuser, S. (2026). Truncating Variants in KIF5C Cause a Milder Disorder Distinct From KIF5C-Associated Cortical Dysplasia. Pediatric Neurology, 179, 37-44. https://doi.org/10.1016/j.pediatrneurol.2026.03.004

MLA:

Kulosik, Luise, et al. "Truncating Variants in KIF5C Cause a Milder Disorder Distinct From KIF5C-Associated Cortical Dysplasia." Pediatric Neurology 179 (2026): 37-44.

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