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

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. Re...

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Autores principales: Filosto, Massimiliano, Piccinelli, Stefano Cotti, Palmieri, Ilaria, Necchini, Nicola, Valente, Marialuisa, Zanella, Isabella, Biasiotto, Giorgio, Lorenzo, Diego Di, Cereda, Cristina, Padovani, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352268/
https://www.ncbi.nlm.nih.gov/pubmed/30583522
http://dx.doi.org/10.3390/jcm8010017
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author Filosto, Massimiliano
Piccinelli, Stefano Cotti
Palmieri, Ilaria
Necchini, Nicola
Valente, Marialuisa
Zanella, Isabella
Biasiotto, Giorgio
Lorenzo, Diego Di
Cereda, Cristina
Padovani, Alessandro
author_facet Filosto, Massimiliano
Piccinelli, Stefano Cotti
Palmieri, Ilaria
Necchini, Nicola
Valente, Marialuisa
Zanella, Isabella
Biasiotto, Giorgio
Lorenzo, Diego Di
Cereda, Cristina
Padovani, Alessandro
author_sort Filosto, Massimiliano
collection PubMed
description 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.
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spelling pubmed-63522682019-02-01 A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome Filosto, Massimiliano Piccinelli, Stefano Cotti Palmieri, Ilaria Necchini, Nicola Valente, Marialuisa Zanella, Isabella Biasiotto, Giorgio Lorenzo, Diego Di Cereda, Cristina Padovani, Alessandro J Clin Med Case Report 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. MDPI 2018-12-22 /pmc/articles/PMC6352268/ /pubmed/30583522 http://dx.doi.org/10.3390/jcm8010017 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Filosto, Massimiliano
Piccinelli, Stefano Cotti
Palmieri, Ilaria
Necchini, Nicola
Valente, Marialuisa
Zanella, Isabella
Biasiotto, Giorgio
Lorenzo, Diego Di
Cereda, Cristina
Padovani, Alessandro
A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome
title A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome
title_full A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome
title_fullStr A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome
title_full_unstemmed A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome
title_short A Novel Mutation in the Stalk Domain of KIF5A Causes a Slowly Progressive Atypical Motor Syndrome
title_sort novel mutation in the stalk domain of kif5a causes a slowly progressive atypical motor syndrome
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352268/
https://www.ncbi.nlm.nih.gov/pubmed/30583522
http://dx.doi.org/10.3390/jcm8010017
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