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.
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Acknowledgments
We thank the patients and her family for their participation in this study.
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Highlights
-A novel KCNJ10 mutation was identified in a patient with non-syndromic ataxia.
-The mutated residue Ile60 interacts with a PIP2 binding site, essential for channel gating
-Screening of KCNJ10 should be implemented in ataxic patients with or without syndromic features
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Nicita, F., Tasca, G., Nardella, M. et al. Novel Homozygous KCNJ10 Mutation in a Patient with Non-syndromic Early-Onset Cerebellar Ataxia. Cerebellum 17, 499–503 (2018). https://doi.org/10.1007/s12311-018-0924-7
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DOI: https://doi.org/10.1007/s12311-018-0924-7