Next Article in Journal
Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation
Previous Article in Journal
Effect of Sarcopenia on Sleep Disturbance in Patients with Chronic Liver Diseases
Article Menu

Export Article

Open AccessCase Report
J. Clin. Med. 2019, 8(1), 17;

A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome

Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy
Genomic and Post-Genomic Center, IRCCS Mondino Fundation, 27100 Pavia, Italy
Department of Molecular and Translational Medicine, University of Brescia, 25100 Brescia, Italy
Clinical Chemistry Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, 25100 Brescia, Italy
These authors equally contributed to the paper.
Author to whom correspondence should be addressed.
Received: 23 November 2018 / Revised: 19 December 2018 / Accepted: 20 December 2018 / Published: 22 December 2018
(This article belongs to the Section Molecular Medicine)
Full-Text   |   PDF [1654 KB, uploaded 22 December 2018]   |  


KIF5A encodes the heavy chain A of kinesin; A motor protein involved in motility functions within neuron. Mutations in the KIF5A N-terminal motor domain are known to cause SPG10; An autosomal dominant hereditary spastic paraplegia (HSP), as well as rare Charcot-Marie-Tooth disease 2 (CMT2) cases. Recently C-terminal cargo-binding tail domain mutations have been associated with an amyotrophic lateral sclerosis (ALS) phenotype. Here we describe a subject presenting with an atypical slowly progressive motor syndrome evolving over a period of 4 years; Characterized by walking difficulties; Muscle hypotrophy mainly involving upper limbs and pyramidal signs confined to the lower limbs. Electromyography demonstrated chronic neurogenic damage and active denervation while electroneurography showed slowly worsening axonal damage. We identified the novel heterozygote variant c.2341A>G in the exon 21 of the KIF5A gene resulting in the amino acid change p.Lys781Glu. The residue Lys781 is located within the terminal region of the stalk domain and is highly evolutionary conserved. Our findings confirm that mutations in KIF5A cause ALS-like phenotypes. However, the stalk domain mutation described here appears to result in an “intermediate” slowly progressive phenotype having aspects resembling ALS as well as HSP and axonal neuropathy. We suggest that KIF5A gene should be considered as a candidate gene in all atypical progressive motor syndromes. View Full-Text
Keywords: ALS; hereditary spastic paraplegias; HSP; KIF5A; SPG10; axonal neuropathy ALS; hereditary spastic paraplegias; HSP; KIF5A; SPG10; axonal neuropathy

Figure 1

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 (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Filosto, M.; Piccinelli, S.C.; Palmieri, I.; Necchini, N.; Valente, M.; Zanella, I.; Biasiotto, G.; Lorenzo, D.D.; Cereda, C.; Padovani, A. A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome. J. Clin. Med. 2019, 8, 17.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top