Expanding the clinical and genetic spectrum of GLUL-related developmental and epileptic encephalopathy.

ABSTRACT: The GLUL gene encodes glutamine synthetase (GS), which plays a crucial role in glutamine-glutamate homeostasis. Both loss-of-function and gain-of-function variants of GLUL are known to cause genetic disorders in humans. Biallelic loss-of-function variants cause congenital glutamine deficiency, leading to developmental and epileptic encephalopathy (DEE) in an autosomal recessive manner. In contrast, certain variants of GLUL that lead to the loss of the N-terminal degron exert a gain-of-function effect, causing an autosomal dominant DEE. Only six autosomal recessive cases and ten autosomal dominant cases have been reported to date, and knowledge about GLUL-related DEE remains limited. In this study, we identified three unrelated patients with DEE carrying heterozygous de novo GLUL variants.

SUBMITTER: Oh DE 

PROVIDER: S-EPMC12518714 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature