Episodic ataxia and severe infantile phenotype in spinocerebellar ataxia type 14: expansion of the phenotype and novel mutations

J Neurol. 2022 Mar;269(3):1476-1484. doi: 10.1007/s00415-021-10712-5. Epub 2021 Jul 22.


Introduction: Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurological disorder characterized by slowly progressive cerebellar ataxia. SCA14 is caused by mutations in PRKCG, a gene encoding protein kinase C gamma (PKCγ), a master regulator of Purkinje cells development.

Methods: We performed next-generation sequencing targeted resequencing panel encompassing 273 ataxia genes in 358 patients with genetically undiagnosed ataxia.

Results: We identified fourteen patients in ten families harboring nine pathogenic heterozygous variants in PRKCG, seven of which were novel. We encountered four patients with not previously described phenotypes: one with episodic ataxia, one with a spastic paraparesis dominating her clinical manifestations, and two children with an unusually severe phenotype.

Conclusions: Our study broadens the genetic and clinical spectrum of SCA14.

Keywords: Broadened phenotype; NGS targeted resequencing panel; Novel mutations; PRKCG; Spinocerebellar ataxia type 14.

MeSH terms

  • Ataxia
  • Female
  • Heterozygote
  • Humans
  • Mutation
  • Phenotype
  • Protein Kinase C / genetics*
  • Spinocerebellar Ataxias* / diagnosis
  • Spinocerebellar Ataxias* / genetics


  • protein kinase C gamma
  • Protein Kinase C

Supplementary concepts

  • Episodic Ataxia