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

• Published in: Journal of clinical medicine 2018-12, Vol.8 (1), p.17
• Main Authors: Filosto, Massimiliano, Piccinelli, Stefano Cotti, Palmieri, Ilaria, Necchini, Nicola, Valente, Marialuisa, Zanella, Isabella, Biasiotto, Giorgio, Lorenzo, Diego Di, Cereda, Cristina, Padovani, Alessandro
• Format: Article
• Language: English
• Subjects: Case Report
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm8010017

encodes the heavy chain A of kinesin; A motor protein involved in motility functions within neuron. Mutations in the 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 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 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 gene should be considered as a candidate gene in all atypical progressive motor syndromes.