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

Francesco Nicita, Giorgio Tasca, Marta Nardella, Emanuele Bellacchio, Ilaria Camponeschi, Gessica Vasco, Tommaso Schirinzi, Enrico Bertini, Ginevra Zanni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)499-503
Number of pages5
JournalCerebellum
Volume17
Issue number4
DOIs
Publication statusPublished - Aug 1 2018

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Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Nicita, F., Tasca, G., Nardella, M., Bellacchio, E., Camponeschi, I., Vasco, G., Schirinzi, T., Bertini, E., & Zanni, G. (2018). Novel Homozygous KCNJ10 Mutation in a Patient with Non-syndromic Early-Onset Cerebellar Ataxia. Cerebellum, 17(4), 499-503. https://doi.org/10.1007/s12311-018-0924-7