Version 1
: Received: 3 July 2024 / Approved: 3 July 2024 / Online: 3 July 2024 (15:27:24 CEST)
How to cite:
Bernard, E.; Cluse, F.; Bohic, A.; Hermier, M.; Raoul, C.; Leblanc, P.; Guissart, C. A Novel de Novo Missense Mutation in KIF1A Associated with Young-Onset Upper-Limb Amyotrophic Lateral Sclerosis. Preprints2024, 2024070355. https://doi.org/10.20944/preprints202407.0355.v1
Bernard, E.; Cluse, F.; Bohic, A.; Hermier, M.; Raoul, C.; Leblanc, P.; Guissart, C. A Novel de Novo Missense Mutation in KIF1A Associated with Young-Onset Upper-Limb Amyotrophic Lateral Sclerosis. Preprints 2024, 2024070355. https://doi.org/10.20944/preprints202407.0355.v1
Bernard, E.; Cluse, F.; Bohic, A.; Hermier, M.; Raoul, C.; Leblanc, P.; Guissart, C. A Novel de Novo Missense Mutation in KIF1A Associated with Young-Onset Upper-Limb Amyotrophic Lateral Sclerosis. Preprints2024, 2024070355. https://doi.org/10.20944/preprints202407.0355.v1
APA Style
Bernard, E., Cluse, F., Bohic, A., Hermier, M., Raoul, C., Leblanc, P., & Guissart, C. (2024). A Novel de Novo Missense Mutation in KIF1A Associated with Young-Onset Upper-Limb Amyotrophic Lateral Sclerosis. Preprints. https://doi.org/10.20944/preprints202407.0355.v1
Chicago/Turabian Style
Bernard, E., Pascal Leblanc and Claire Guissart. 2024 "A Novel de Novo Missense Mutation in KIF1A Associated with Young-Onset Upper-Limb Amyotrophic Lateral Sclerosis" Preprints. https://doi.org/10.20944/preprints202407.0355.v1
Abstract
Objectives: To investigate the etiology of amyotrophic lateral sclerosis (ALS) in an adult female patient. Methods: We conducted trio genome sequencing on a 35-year-old woman with progressive weakness in her left upper limb, as well as on her parents. Prior to sequencing, we performed a comprehensive neurological work-up on the patient, including neurological exam, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Results : The propositus experienced weakness and atrophy in her left hand 6 months before the evaluation. This was associated with brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Genome trio sequencing identified a likely pathogenic de novo variant in the propositus’s KIF1A gene (NM_001244008.2): c.574A>G, p.(Ile192Val). Discussion: Pathogenic variants in the KIF1A gene have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). The present report describe a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.
Keywords
Amyotrophic Lateral Sclerosis; Genome sequencing; KIF1A; de novo mutation
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
