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


Journal

Neurogenetics
ISSN: 1364-6753
Titre abrégé: Neurogenetics
Pays: United States
ID NLM: 9709714

Informations de publication

Date de publication:
01 2022
Historique:
received: 03 03 2021
accepted: 01 08 2021
pubmed: 4 11 2021
medline: 17 3 2022
entrez: 3 11 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34731330
doi: 10.1007/s10048-021-00666-1
pii: 10.1007/s10048-021-00666-1
pmc: PMC8782781
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

27-35

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

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Auteurs

Berardo Rinaldi (B)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Yu-Han Ge (YH)

Ministry of Education Key Laboratory of Model Animal for Disease Study, Department of Neurology, Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.
State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Institute for Brain Sciences, Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, China.

Elena Freri (E)

Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.

Arianna Tucci (A)

Clinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK. a.tucci@qmul.ac.uk.

Tiziana Granata (T)

Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.

Margherita Estienne (M)

Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.

Jia-Hui Sun (JH)

Ministry of Education Key Laboratory of Model Animal for Disease Study, Department of Neurology, Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.
State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Institute for Brain Sciences, Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, China.

Bénédicte Gérard (B)

Laboratoires de diagnostic génétique, Institut Medical d'Alsace, Hôpitaux Universitaire de Strasbourg, Strasbourg, France.

Allan Bayat (A)

Department for Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark.
Institute for Regional Health Services Research, University of Southern Denmark, Odense, Denmark.

Stephanie Efthymiou (S)

Department of Neuromuscular disorders, UCL Queen Square Institute of Neurology, London, UK.

Cristina Gervasini (C)

Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.

Yun Stone Shi (YS)

Ministry of Education Key Laboratory of Model Animal for Disease Study, Department of Neurology, Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China. yunshi@nju.edu.cn.
State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Institute for Brain Sciences, Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, China. yunshi@nju.edu.cn.

Henry Houlden (H)

Department of Neuromuscular disorders, UCL Queen Square Institute of Neurology, London, UK.

Paola Marchisio (P)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Donatella Milani (D)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

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Classifications MeSH