{Reference Type}: Journal Article
{Title}: 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.
{Author}: Maillard PY;Baer S;Schaefer É;Desnous B;Villeneuve N;Lépine A;Fabre A;Lacoste C;El Chehadeh S;Piton A;Porter LF;Perriard C;Wardé MA;Spitz MA;Laugel V;Lesca G;Putoux A;Ville D;Mignot C;Héron D;Nabbout R;Barcia G;Rio M;Roubertie A;Meyer P;Paquis-Flucklinger V;Patat O;Lefranc J;Gerard M; ;de Bellescize J;Villard L;De Saint Martin A;Milh M;
{Journal}: Epilepsia
{Volume}: 63
{Issue}: 10
{Year}: 10 2022
{Factor}: 6.74
{DOI}: 10.1111/epi.17336
{Abstract}: 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.