Gain-of-function variants in GABRD reveal a novel pathway for neurodevelopmental disorders and epilepsy.

ABSTRACT: A potential link between GABRD encoding the δ subunit of extrasynaptic GABAA receptors and neurodevelopmental disorders has largely been disregarded due to conflicting conclusions from early studies. However, we identified seven heterozygous missense GABRD variants in 10 patients with neurodevelopmental disorders and generalized epilepsy. One variant occurred in two sibs of healthy parents with presumed somatic mosaicism, another segregated with the disease in three affected family members, and the remaining five occurred de novo in sporadic patients. Electrophysiological measurements were used to determine the functional consequence of the seven missense δ subunit variants in receptor combinations of α1β3δ and α4β2δ GABAA receptors. This was accompanied by analysis of electroclinical phen

SUBMITTER: Ahring PK 

PROVIDER: S-EPMC9630717 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature