Trio exome analysis is a valuable tool for genetic diagnosis of epilepsy in Mali

Trio exome sequencing is widely used for various disorders. We investigated the utility of this method to identify genetic causes of epilepsy in Mali.

We enrolled patients with epilepsy suspected of an underlying genetic etiology. Exome sequencing data from those with a minimum of a trio (proband and both biological parents) were analyzed to identify and classify potential causative genetic variants.

We sequenced 159 individuals, including 57 patients with epilepsy from 42 families, the largest trio sequencing cohort for epilepsy in sub-Saharan Africa. Of these, 16 families (38%) received a putative molecular diagnosis, with autosomal recessive inheritance seen in 7 of 16 (44%) and de novo events in 9 of 16 (56%). The 17 total variants were classified as pathogenic (n = 8) or likely pathogenic (n = 9), with 14 of 17 (82%) being novel to public databases. An additional 6 of 42 families (14%) had variants of uncertain significance with consistent genotype-phenotype correlations. There were no common candidate genes across families.

Our findings illuminate a significant genetic contribution to epilepsy in Mali with a substantial genetic heterogeneity, as well as the utility of trio exome sequencing for efficient diagnosis. This further emphasizes the persistent and critical need for greater inclusivity in genomic research and implementation.