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.

Novel homozygous KCNJ10 mutation in a patient with non-syndromic early-onset cerebellar ataxia / Nicita, Francesco; Tasca, Giorgio; Nardella, Marta; Bellacchio, Emanuele; Camponeschi, Ilaria; Vasco, Gessica; Schirinzi, Tommaso; Bertini, Enrico; Zanni, Ginevra. - In: THE CEREBELLUM. - ISSN 1473-4222. - STAMPA. - 17:4(2018), pp. 499-503. [10.1007/s12311-018-0924-7]

Novel homozygous KCNJ10 mutation in a patient with non-syndromic early-onset cerebellar ataxia

CAMPONESCHI, ILARIA
;
2018

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.
2018
Ataxia; EAST syndrome; epilepsy; KCNJ10; Kir4.1; Phosphatidylinositol 4, 5-bisphosphate (PIP2); Neurology; Neurology (clinical)
01 Pubblicazione su rivista::01i Case report
Novel homozygous KCNJ10 mutation in a patient with non-syndromic early-onset cerebellar ataxia / Nicita, Francesco; Tasca, Giorgio; Nardella, Marta; Bellacchio, Emanuele; Camponeschi, Ilaria; Vasco, Gessica; Schirinzi, Tommaso; Bertini, Enrico; Zanni, Ginevra. - In: THE CEREBELLUM. - ISSN 1473-4222. - STAMPA. - 17:4(2018), pp. 499-503. [10.1007/s12311-018-0924-7]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1117069
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