10.5061/DRYAD.S7H44J15S
Gecz, Jozef
0000-0002-2648-7828
University of Adelaide
Heron, Sarah
University of Adelaide
Clinical data for individuals from families with SLC32A1 variants
Dryad
dataset
2020
2022-02-09T00:00:00Z
2022-02-09T00:00:00Z
en
31390 bytes
3
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Objective: To identify the causative gene in a large unsolved family with
genetic epilepsy with febrile seizures plus (GEFS+), we sequenced the
genomes of family members, and then determined the contribution of the
identified gene to the pathogenicity of epilepsies by examining sequencing
data from 2772 additional patients. Methods: We performed whole genome
sequencing of three members of a GEFS+ family. Subsequently, whole exome
sequencing (ES) data from 1165 epilepsy patients from the Epi4K dataset
and 1329 Australian epilepsy patients from the Epi25 dataset was
interrogated. Targeted resequencing was performed on 278 patients with FS
or GEFS+ phenotypes. Variants were validated and familial segregation
examined by Sanger sequencing. Results: Eight previously unreported
missense variants were identified in SLC32A1, coding for the vesicular
inhibitory amino acid co-transporter VGAT. Two variants co- segregated
with the phenotype in two large GEFS+ families containing eight and ten
affected individuals, respectively. Six further variants were identified
in smaller families with GEFS+ or idiopathic generalized epilepsy (IGE).
Conclusions: Missense variants in SLC32A1 cause GEFS+ and IGE. These
variants are predicted to alter GABA transport into synaptic vesicles,
leading to altered neuronal inhibition. Examination of further epilepsy
cohorts will determine the full genotype-phenotype spectrum associated
with SLC32A1 variants.