Familial epilepsy – clinical-epidemiological characteristics and next-generation sequencing in the Republic of Moldova’s population

Abstract

Background: Although several theories are implicated in the origin of epilepsy, its cause is still unknown in about 50% of cases. To associate a gene with epilepsy for the first time, families with multiple affected members are needed. The aim of our study is carrying out a clinical-genetic study of multiplex families from the Republic of Moldova, for estimating the genetic biomarkers and establishing their weight in epileptogenesis. Material and methods: An epidemiological, descriptive study (2018 – 2023) started with lancing a National Epilepsy Registry for multiplex families. Whole Exome Sequencing (WES) was performed on the first 11 families. Preliminary statistical methods were applied. Results: Our National registry counts now 74 families including 186 members. First 11 families’ WES results showed that the most involved chromosomes with candidate epileptogenic variants are the 1, 2, 3, 4, 7, 12, and 17. Top affected genes are the AUTS2, ATXN1, KCNMA1, IRF2BPL, SUFU, CENPE, SACS, EDC3, RYR2, ANKRD11, PTPRD, CHL1, MYH1, CC2D2A, LIAS, TBCD and AARS. From all the detected variants, 20.3% were classified as deleterious and probably pathogenic, 38.9% were marked as tolerated and benign and 22.8% were variants of unknown significance (VUS). Conclusions: Our results represent an absolute novelty for our country, such studies having been never previously performed. Subjects continue to be recruited and the National Register of presumed genetic epilepsy is constantly being updated.