Novel Homozygous KCNJ10 Mutation in a Patient with Non-syndromic Early-Onset Cerebellar Ataxia

Cerebellum. 2018 Aug;17(4):499-503. doi: 10.1007/s12311-018-0924-7.

Abstract

Mutations in KCNJ10, which encodes the inwardly rectifying potassium channel Kir4.1, a primary regulator of membrane excitability and potassium homeostasis, cause a complex syndrome characterized by seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance called SeSAME/EAST syndrome. We describe a 41-year-old patient with non-syndromic, slowly progressive, early-onset ataxia. Targeted next-generation sequencing identified a novel c.180 T > G (p.Ile60Met) missense homozygous mutation. The mutated residue Ile60Met likely impairs phosphatidylinositol 4, 5-bisphosphate (PIP2) binding which is known to play an essential role in channel gating. Our study expands the clinical and mutational spectrum of KCNJ10-related disorders and suggests that screening of this gene should be implemented in patients with early-onset ataxia, with or without syndromic features.

Keywords: Ataxia; EAST syndrome; Epilepsy; KCNJ10; Kir4.1; Phosphatidylinositol 4, 5-bisphosphate (PIP2).

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Female
  • Homozygote
  • Humans
  • Models, Molecular
  • Mutation, Missense*
  • Phenotype
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Spinocerebellar Degenerations / diagnostic imaging
  • Spinocerebellar Degenerations / genetics*
  • Spinocerebellar Degenerations / physiopathology

Substances

  • Kcnj10 (channel)
  • Potassium Channels, Inwardly Rectifying