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

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 2018

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Spinocerebellar Degenerations
Ataxia
Mutation
Inwardly Rectifying Potassium Channel
Deafness
Missense Mutation
Phosphatidylinositols
Intellectual Disability
Electrolytes
Potassium
Seizures
Homeostasis
Membranes
Genes
SeSAME syndrome

Cite this

@article{7488db01c175498b9eb9a6219ef21dd4,
title = "Novel Homozygous KCNJ10 Mutation in a Patient with Non-syndromic Early-Onset Cerebellar Ataxia",
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.",
author = "Francesco Nicita and Giorgio Tasca and Marta Nardella and Emanuele Bellacchio and Ilaria Camponeschi and Gessica Vasco and Tommaso Schirinzi and Enrico Bertini and Ginevra Zanni",
year = "2018",
month = "8",
doi = "10.1007/s12311-018-0924-7",
language = "English",
volume = "17",
pages = "499--503",
journal = "Cerebellum",
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publisher = "Springer New York",
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TY - JOUR

T1 - Novel Homozygous KCNJ10 Mutation in a Patient with Non-syndromic Early-Onset Cerebellar Ataxia

AU - Nicita, Francesco

AU - Tasca, Giorgio

AU - Nardella, Marta

AU - Bellacchio, Emanuele

AU - Camponeschi, Ilaria

AU - Vasco, Gessica

AU - Schirinzi, Tommaso

AU - Bertini, Enrico

AU - Zanni, Ginevra

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

U2 - 10.1007/s12311-018-0924-7

DO - 10.1007/s12311-018-0924-7

M3 - Article

C2 - 29476442

VL - 17

SP - 499

EP - 503

JO - Cerebellum

JF - Cerebellum

SN - 1473-4222

IS - 4

ER -