Banerjee, Santasree;
Zhao, Qiang;
Wang, Bo;
Qin, Jiale;
Yuan, Xin;
Lou, Ziwei;
Zheng, Weizeng;
... Li, Chen; + view all
(2024)
A novel in-frame deletion in KIF5C gene causes infantile onset epilepsy and psychomotor retardation.
MedComm
, 5
(4)
, Article e469. 10.1002/mco2.469.
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Abstract
Motor proteins, encoded by Kinesin superfamily (KIF) genes, are critical for brain development and plasticity. Increasing studies reported KIF’s roles in neurodevelopmental disorders. Here, a 6 years and 3 months-old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease-related family history. Whole exome sequencing identified a novel heterozygous in-frame deletion (c.265_267delTCA) in exon 3 of the KIF5C in the proband, resulting in the removal of evolutionarily highly conserved p.Ser90, located in its ATP-binding domain. Sanger sequencing excluded the proband's parents and family members from harboring this variant. The activity of ATP hydrolysis in vitro was significantly reduced as predicted. Immunofluorescence studies showed wild-type KIF5C was widely distributed throughout the cytoplasm, while mutant KIF5C was colocalized with microtubules. The live-cell imaging of the cargo-trafficking assay revealed that mutant KIF5C lost the peroxisome-transporting ability. Drosophila models also confirmed p.Ser90del's essential role in nervous system development. This study emphasized the importance of the KIF5C gene in intracellular cargo-transport as well as germline variants that lead to neurodevelopmental disorders and might enable clinicians for timely and accurate diagnosis and disease management in the future.
| Type: | Article |
|---|---|
| Title: | A novel in-frame deletion in KIF5C gene causes infantile onset epilepsy and psychomotor retardation |
| Location: | China |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/mco2.469 |
| Publisher version: | http://dx.doi.org/10.1002/mco2.469 |
| Language: | English |
| Additional information: | Copyright © 2024 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd. This is an open access article under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Cargo trafficking, Drosophila model, infantile-onset epilepsy, in-frame deletion, Kinesin, psychomotor retardation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10190327 |
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