GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. A novel syndrome related to GAD67 deficiency is characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele. Association of bi-allelic variants in GAD1 with a novel syndrome characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele provides evidence of the essential role of the GAD67 enzyme during human foetal development. Bi-allelic loss-of-function variants in humans fully recapitulate the association of epilepsy, cleft palate and omphalocele observed in animal models.
GAD1