Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Rossella Spataro, Antonio Canosa, Tiziana Colletti, Vincenzo La Bella, Antonio Ilardi, Christian Lunetta, Gioacchino Tedeschi, Maria Francesca Pisano, Paolo Volanti

Risultato della ricerca: Articlepeer review

312 Citazioni (Scopus)


To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
Lingua originaleEnglish
pagine (da-a)1268-1283.e5
Numero di pagine22
Stato di pubblicazionePublished - 2018

All Science Journal Classification (ASJC) codes

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