Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy

Morad Kamand; Reema Taleb; Methi Wathikthinnakon; Fadumo Abdullahi Mohamed; Said Pasalar Ghazanfari; Denis Konstantinov; Jonas Laugård Hald; Bjørn Holst; Charlotte Brasch-Andersen; Rikke S Møller; Johannes R Lemke; Ilona Krey; Kristine Freude; Abinaya Chandrasekaran

doi:10.1016/j.scr.2024.103372

Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy

Morad Kamand, Reema Taleb, Methi Wathikthinnakon, Fadumo Abdullahi Mohamed, Said Pasalar Ghazanfari, Denis Konstantinov, Jonas Laugård Hald, Bjørn Holst, Charlotte Brasch-Andersen, Rikke S Møller, Johannes R Lemke, Ilona Krey, Kristine Freude, Abinaya Chandrasekaran^*

^*Corresponding author af dette arbejde

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

Abstract

Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ahring et al. (2022) showed a variant in the gene that encodes the delta subunit (GABRD) is strongly associated with the gain-of-function of extrasynaptic GABAAR. Here, we report the generation of two patient-specific human induced pluripotent stem cells (hiPSC) lines with (i) a de novo variant and (ii) a maternal variant, both for the pathogenic GABRD c.872 C>T, (p.T291I). The variants in the generated cell line were corrected using the CRISPR-Cas9 gene editing technique (respective isogenic control lines).

Originalsprog	Engelsk
Artikelnummer	103372
Tidsskrift	Stem Cell Research
Vol/bind	76
DOI	https://doi.org/10.1016/j.scr.2024.103372
Status	Udgivet - apr. 2024

Bibliografisk note

Adgang til dokumentet

10.1016/j.scr.2024.103372

Citationsformater

Kamand, M., Taleb, R., Wathikthinnakon, M., Mohamed, F. A., Ghazanfari, S. P., Konstantinov, D., Hald, J. L., Holst, B., Brasch-Andersen, C., Møller, R. S., Lemke, J. R., Krey, I., Freude, K., & Chandrasekaran, A. (2024). Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy. Stem Cell Research, 76, Artikel 103372. https://doi.org/10.1016/j.scr.2024.103372

@article{732d13ba641b4f9a99b6745f22b50744,

title = "Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy",

abstract = "Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ahring et al. (2022) showed a variant in the gene that encodes the delta subunit (GABRD) is strongly associated with the gain-of-function of extrasynaptic GABAAR. Here, we report the generation of two patient-specific human induced pluripotent stem cells (hiPSC) lines with (i) a de novo variant and (ii) a maternal variant, both for the pathogenic GABRD c.872 C>T, (p.T291I). The variants in the generated cell line were corrected using the CRISPR-Cas9 gene editing technique (respective isogenic control lines).",

keywords = "Humans, Receptors, GABA-A/genetics, Induced Pluripotent Stem Cells/metabolism, Epilepsy/genetics, Mutation, Missense, Gene Editing",

author = "Morad Kamand and Reema Taleb and Methi Wathikthinnakon and Mohamed, {Fadumo Abdullahi} and Ghazanfari, {Said Pasalar} and Denis Konstantinov and Hald, {Jonas Laug{\aa}rd} and Bj{\o}rn Holst and Charlotte Brasch-Andersen and M{\o}ller, {Rikke S} and Lemke, {Johannes R} and Ilona Krey and Kristine Freude and Abinaya Chandrasekaran",

note = "Copyright {\textcopyright} 2024. Published by Elsevier B.V.",

year = "2024",

month = apr,

doi = "10.1016/j.scr.2024.103372",

language = "English",

volume = "76",

journal = "Stem Cell Research",

issn = "1873-5061",

publisher = "Elsevier B.V.",

}

Kamand, M, Taleb, R, Wathikthinnakon, M, Mohamed, FA, Ghazanfari, SP, Konstantinov, D, Hald, JL, Holst, B, Brasch-Andersen, C, Møller, RS, Lemke, JR, Krey, I, Freude, K & Chandrasekaran, A 2024, 'Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy', Stem Cell Research, bind 76, 103372. https://doi.org/10.1016/j.scr.2024.103372

TY - JOUR

T1 - Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy

AU - Kamand, Morad

AU - Taleb, Reema

AU - Wathikthinnakon, Methi

AU - Mohamed, Fadumo Abdullahi

AU - Ghazanfari, Said Pasalar

AU - Konstantinov, Denis

AU - Hald, Jonas Laugård

AU - Holst, Bjørn

AU - Brasch-Andersen, Charlotte

AU - Møller, Rikke S

AU - Lemke, Johannes R

AU - Krey, Ilona

AU - Freude, Kristine

AU - Chandrasekaran, Abinaya

PY - 2024/4

Y1 - 2024/4

N2 - Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ahring et al. (2022) showed a variant in the gene that encodes the delta subunit (GABRD) is strongly associated with the gain-of-function of extrasynaptic GABAAR. Here, we report the generation of two patient-specific human induced pluripotent stem cells (hiPSC) lines with (i) a de novo variant and (ii) a maternal variant, both for the pathogenic GABRD c.872 C>T, (p.T291I). The variants in the generated cell line were corrected using the CRISPR-Cas9 gene editing technique (respective isogenic control lines).

AB - Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ahring et al. (2022) showed a variant in the gene that encodes the delta subunit (GABRD) is strongly associated with the gain-of-function of extrasynaptic GABAAR. Here, we report the generation of two patient-specific human induced pluripotent stem cells (hiPSC) lines with (i) a de novo variant and (ii) a maternal variant, both for the pathogenic GABRD c.872 C>T, (p.T291I). The variants in the generated cell line were corrected using the CRISPR-Cas9 gene editing technique (respective isogenic control lines).

KW - Humans

KW - Receptors, GABA-A/genetics

KW - Induced Pluripotent Stem Cells/metabolism

KW - Epilepsy/genetics

KW - Mutation, Missense

KW - Gene Editing

U2 - 10.1016/j.scr.2024.103372

DO - 10.1016/j.scr.2024.103372

M3 - Article

C2 - 38458029

SN - 1873-5061

VL - 76

JO - Stem Cell Research

JF - Stem Cell Research

M1 - 103372

ER -

Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy

Abstract

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