%0 Journal Article
%T Molecular and clinical descriptions of patients with GABAA receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype-phenotype correlation.
%A Maillard PY
%A Baer S
%A Schaefer É
%A Desnous B
%A Villeneuve N
%A Lépine A
%A Fabre A
%A Lacoste C
%A El Chehadeh S
%A Piton A
%A Porter LF
%A Perriard C
%A Wardé MA
%A Spitz MA
%A Laugel V
%A Lesca G
%A Putoux A
%A Ville D
%A Mignot C
%A Héron D
%A Nabbout R
%A Barcia G
%A Rio M
%A Roubertie A
%A Meyer P
%A Paquis-Flucklinger V
%A Patat O
%A Lefranc J
%A Gerard M
%A  
%A de Bellescize J
%A Villard L
%A De Saint Martin A
%A Milh M
%J Epilepsia
%V 63
%N 10
%D 10 2022
%M 35718920
%F 6.74
%R 10.1111/epi.17336
%X γ-Aminobutyric acid (GABA)A -receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming better known. Because of the common molecular structure and physiological role of these phenotypes, it seemed interesting to describe a putative phenotype associated with GABAA -receptor-related disorders as a whole and seek possible genotype-phenotype correlations.<BR>We collected clinical, electrophysiological, therapeutic, and molecular data from patients with GABAA -receptor subunit variants (GABRA1, GABRB2, GABRB3, and GABRG2) through a national French collaboration using the EPIGENE network and compared these data to the one already described in the literature.<BR>We gathered the reported patients in three epileptic phenotypes: 15 patients with fever-related epilepsy (40%), 11 with early developmental epileptic encephalopathy (30%), 10 with generalized epilepsy spectrum (27%), and 1 patient without seizures (3%). We did not find a specific phenotype for any gene, but we showed that the location of variants on the transmembrane (TM) segment was associated with a more severe phenotype, irrespective of the GABAA -receptor subunit gene, whereas N-terminal variants seemed to be related to milder phenotypes.<BR>GABAA -receptor subunit variants are associated with highly variable phenotypes despite their molecular and physiological proximity. None of the genes described here was associated with a specific phenotype. On the other hand, it appears that the location of the variant on the protein may be a marker of severity. Variant location may have important weight in the development of targeted therapeutics.