Expanding the spectrum of KIF5A mutations—case report of a large kindred with familial ALS and overlapping syndrome

JarosŁaw Dulski, Audrey J. Strongosky, Rana Hanna Al-Shaikh, Zbigniew K. Wszolek

Research output: Contribution to journalArticlepeer-review


Objectives: This paper presents the first report of amyotrophic lateral sclerosis (ALS) kindred due to the KIF5A p.Arg1007Lys, a splice-altering variant. Methods: An index case was a 54-year-old male who developed progressive gait difficulty and imbalance followed by mild parkinsonism, spasticity, neuropathy, ataxia, and cognitive impairment with predominant subcortical frontal involvement. Brain MRI showed marked bilateral parietal lobes atrophy. Electromyography demonstrated chronic diffuse neurogenic changes. Due to the positive history of similar symptoms in his father and the diagnosis of ALS in 10 other family members, extensive genetic testing was pursued. Results: Genetic screening for GRN, C9orf72, TARDBP, SOD1, FUS, MAPT mutations, and hereditary ataxia panel, was unremarkable. Whole-exome sequencing revealed c.3020G > A (p.Arg1007Lys) mutation in the KIF5A gene, later confirmed in two affected relatives. Discussion: Similar to previous reports on KIF5A-related ALS, our index case, had a mild disease course with prolonged survival. However, as the rate of progression and survival time differed even among the same family members, other factors were probably at play. Additionally, our index case and his father displayed features overlapping ALS, spastic paraplegia, Charcot-Marie-Tooth disease type 2, and frontotemporal dementia. Therefore, we suggest considering KIF5A mutations in the differential diagnosis, particularly in the presence of overlapping features of spasticity, neuropathy, cerebellar ataxia, and dementia.

Original languageEnglish (US)
Pages (from-to)347-350
Number of pages4
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Issue number3-4
StatePublished - 2023


  • Amyotrophic lateral sclerosis
  • Charcot-Marie-Tooth
  • DNA
  • frontotemporal dementia
  • genetics
  • spastic paraplegia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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