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Open Access 01-01-2022 | Disorders of Intellectual Development | Original Article

Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene

Authors: Berardo Rinaldi, Yu-Han Ge, Elena Freri, Arianna Tucci, Tiziana Granata, Margherita Estienne, Jia-Hui Sun, Bénédicte Gérard, Allan Bayat, Stephanie Efthymiou, Cristina Gervasini, Yun Stone Shi, Henry Houlden, Paola Marchisio, Donatella Milani

Published in: Neurogenetics | Issue 1/2022

Abstract

AMPA-type glutamate receptors (AMPARs) are postsynaptic ionotropic receptors which mediate fast excitatory currents. AMPARs have a heterotetrameric structure, variably composed by the four subunits GluA1-4 which are encoded by genes GRIA1-4. Increasing evidence support the role of pathogenic variants in GRIA1-4 genes as causative for syndromic intellectual disability (ID). We report an Italian pedigree where some male individuals share ID, seizures and facial dysmorphisms. The index subject was referred for severe ID, myoclonic seizures, cerebellar signs and short stature. Whole exome sequencing identified a novel variant in GRIA3, c.2360A > G, p.(Glu787Gly). The GRIA3 gene maps to chromosome Xq25 and the c.2360A > G variant was transmitted by his healthy mother. Subsequent analysis in the family showed a segregation pattern compatible with the causative role of this variant, further supported by preliminary functional insights. We provide a detailed description of the clinical evolution of the index subjects and stress the relevance of myoclonic seizures and cerebellar syndrome as cardinal features of his presentation.

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Title: Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene
Authors: Berardo Rinaldi
Yu-Han Ge
Elena Freri
Arianna Tucci
Tiziana Granata
Margherita Estienne
Jia-Hui Sun
Bénédicte Gérard
Allan Bayat
Stephanie Efthymiou
Cristina Gervasini
Yun Stone Shi
Henry Houlden
Paola Marchisio
Donatella Milani
Publication date: 01-01-2022
Publisher: Springer Berlin Heidelberg
Keywords: Disorders of Intellectual Development
Intellectual Disability
Status Epilepticus
Published in: Neurogenetics / Issue 1/2022
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-021-00666-1

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Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene

Abstract

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Abstract

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