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

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

doi:10.1007/s10048-021-00666-1

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

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

^*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstrakt

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.

Originalsprog	Engelsk
Tidsskrift	Neurogenetics
Vol/bind	23
Sider (fra-til)	27-35
ISSN	1364-6745
DOI	https://doi.org/10.1007/s10048-021-00666-1
Status	Udgivet - jan. 2022

Bibliografisk note

Funding Information:
This work is supported by grants from National Key R & D Program of China (2019YFA0801603 to Y.S.S.), the National Natural Science Foundation of China (91849112 to Y.S.S), the Natural Science Foundation of Jiangsu Province (BE2019707 to Y.S.S.) and Fundamental Research Funds for the Central Universities (0903–14380029 to Y.S.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2021, The Author(s).

Dokumenter og links

10.1007/s10048-021-00666-1Licens: CC BY

Open Access VersionForlagets udgivne version, 1,32 MBLicens: CC BY

Citationsformater

Rinaldi, B., Ge, Y. H., Freri, E., Tucci, A., Granata, T., Estienne, M., Sun, J. H., Gérard, B., Bayat, A., Efthymiou, S., Gervasini, C., Shi, Y. S., Houlden, H., Marchisio, P., & Milani, D. (2022). Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene. Neurogenetics, 23, 27-35. https://doi.org/10.1007/s10048-021-00666-1

Rinaldi, Berardo ; Ge, Yu Han ; Freri, Elena ; Tucci, Arianna ; Granata, Tiziana ; Estienne, Margherita ; Sun, Jia Hun ; Gérard, Bénédicte ; Bayat, Allan ; Efthymiou, Stephanie ; Gervasini, Cristina ; Shi, Yun Stone ; Houlden, Henry ; Marchisio, Paola ; Milani, Donatella. / Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene. I: Neurogenetics. 2022 ; Bind 23. s. 27-35.

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title = "Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene",

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.",

keywords = "AMPARs, Cerebellar hypoplasia, Glutamate, GRIA3, Myoclonic status epilepticus",

author = "Berardo Rinaldi and Ge, {Yu Han} and Elena Freri and Arianna Tucci and Tiziana Granata and Margherita Estienne and Sun, {Jia Hun} and B{\'e}n{\'e}dicte G{\'e}rard and Allan Bayat and Stephanie Efthymiou and Cristina Gervasini and Shi, {Yun Stone} and Henry Houlden and Paola Marchisio and Donatella Milani",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = jan,

doi = "10.1007/s10048-021-00666-1",

language = "English",

volume = "23",

pages = "27--35",

journal = "Neurogenetics",

issn = "1364-6745",

publisher = "Heinemann",

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Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene. / Rinaldi, Berardo; Ge, Yu Han; Freri, Elena; Tucci, Arianna; Granata, Tiziana; Estienne, Margherita; Sun, Jia Hun; Gérard, Bénédicte; Bayat, Allan; Efthymiou, Stephanie; Gervasini, Cristina; Shi, Yun Stone; Houlden, Henry; Marchisio, Paola; Milani, Donatella.

I: Neurogenetics, Bind 23, 01.2022, s. 27-35.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene

AU - Rinaldi, Berardo

AU - Ge, Yu Han

AU - Freri, Elena

AU - Tucci, Arianna

AU - Granata, Tiziana

AU - Estienne, Margherita

AU - Sun, Jia Hun

AU - Gérard, Bénédicte

AU - Bayat, Allan

AU - Efthymiou, Stephanie

AU - Gervasini, Cristina

AU - Shi, Yun Stone

AU - Houlden, Henry

AU - Marchisio, Paola

AU - Milani, Donatella

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

KW - AMPARs

KW - Cerebellar hypoplasia

KW - Glutamate

KW - GRIA3

KW - Myoclonic status epilepticus

U2 - 10.1007/s10048-021-00666-1

DO - 10.1007/s10048-021-00666-1

M3 - Journal article

C2 - 34731330

AN - SCOPUS:85118528582

VL - 23

SP - 27

EP - 35

JO - Neurogenetics

JF - Neurogenetics

SN - 1364-6745

ER -

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

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Bibliografisk note

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