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Title: Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants
Author: Neuray, Caroline
Maroofian, Reza
Scala, Marcello
Sultan, Tipu
Pai, Gurpur S.
Mojarrad, Majid
El Khashab, Heba
deHoll, Leigh
Yue, Wyatt
Alsaif, Hessa S.
Zanetti, Maria N.
Bello, Oscar
Person, Richard
Eslahi, Atieh
Khazaei, Zaynab
Feizabadi, Masoumeh H
Efthymiou, Stephanie
SYNaPS Study Group
El Bassyouni, Hala T.
Soliman, Doaa R.
Tekes, Selahattin
Ozer, Leyla
Baltaci, Volkan
Khan, Suliman
Beetz, Christian
Amr, Khalda S.
Salpietro, Vicenzo
Jamshidi, Yalda
Alkuraya, Fowzan S.
Houlden, Henry
Cormand Rifà, Bru
Keywords: Epilèpsia
Malalties cerebrals
Brain diseases
Issue Date: 23-Jul-2020
Publisher: Oxford University Press
Abstract: Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.
Note: Reproducció del document publicat a:
It is part of: Brain, 2020, vol. 143, num. 8, p. 2388-2397
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ISSN: 0006-8950
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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