ArticleScientific reports2018
A novel homozygous mutation in GAD1 gene described in a schizophrenic patient impairs activity and dimerization of GAD67 enzyme.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders.International journal of molecular sciences · 2025Review
- Influence of Glutamate Neurotransmission Genes on the Outcomes of Antipsychotic Treatments.Pharmacopsychiatry · 2025Article
- A signal transduction blind spot: the function of adenylyl cyclase transmembrane domains.The FEBS journal · 2025Review
- Sigma-1 Receptor Activation by Fluvoxamine Ameliorates ER Stress, Synaptic Dysfunction and Behavioral Deficits in a Ketamine Model of Schizophrenia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Causes and countermeasures for the increased infection and COVID-19 mortality rates in patients with schizophrenia.IBRO neuroscience reports · 2024Review
- Interaction between Oligodendrocytes and Interneurons in Brain Development and Related Neuropsychiatric Disorders.International journal of molecular sciences · 2024Review
- The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.International journal of molecular sciences · 2024Review
- Beyond the γ-aminobutyric acid hypothesis of schizophrenia.Frontiers in cellular neuroscience · 2023Review
- Picrotoxin Delineates Different Transport Configurations for Malate and γ Aminobutyric Acid through TaALMT1.Biology · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- BDNF and JNK Signaling Modulate Cortical Interneuron and Perineuronal Net Development: Implications for Schizophrenia-Linked 16p11.2 Duplication Syndrome.Schizophrenia bulletin · 2021Article
- Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice.Molecular brain · 2021Article
- CRISPR/Cas9-engineered Gad1 elimination in rats leads to complex behavioral changes: implications for schizophrenia.Translational psychiatry · 2020Article
- Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants.Brain : a journal of neurology · 2020Article
- Neurological Syndromes Associated with Anti-GAD Antibodies.International journal of molecular sciences · 2020Review
- Rare compound heterozygous missenseNeuropsychiatric disease and treatment · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Recently, by whole exome sequencing of schizophrenia (SCZ) patients, we identified a subject that was homozygous for a novel missense substitution (c.391 A > G) in the glutamate acid decarboxylase 1 (GAD1) gene. GAD1 encodes for GAD67 enzyme, catalyzing the production of gamma-aminobutyric acid (GABA) from L-glutamic acid. Here, we studied the impact of this mutation on GAD67 activity, dimerization and subcellular localization. Biochemical assay revealed that c.391 A > G reduces GAD67 enzymatic activity by ~30%, probably due to the impaired homodimerization of homozygous mutants as highlighted by proximity ligation assays. The mutational screening of 120 genes of the "GABAergic system" in a cohort of 4,225 SCZ cases and 5,834 controls (dbGaP: phs000473.v1.p2), did not identify other cases that were homozygous for ultra-rare variants in GAD1, but highlighted an increased frequency of cases that were homozygous for rare variants in genes of the GABA system (SCZ: 0.14% vs. Controls: 0.00%; p-value = 0.0055). In conclusion, this study demonstrates the functional impact of c.391 A > G variant and its biological effect makes it a good candidate as risk variant for SCZ. This study also supports an involvement of ultra-rare variants in GABAergic genes in the etiopathogenesis of SCZ.
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