We report an in-depth genetic analysis in an 11-year-old boy with drug-resistant, generalized seizures and developmental disability. Three distinct variants of unknown clinical significance (VUS) were detected by whole exome sequencing (WES) but not by initial genetic analyses (microarray and epilepsy gene panel). These variants involve the SLC7A3, CACNA1H, and IGLON5 genes, which were subsequently evaluated by computational analyses using the InterVar tool and MutationTaster. While future functional studies are necessary to prove the pathogenicity of a certain VUS, segregation analyses over three generations and in silico predictions suggest the X-linked gene SLC7A3 (transmembrane solute carrier transporter) as the likely culprit gene in this patient. In addition, a search via GeneMatcher unveiled two additional patients with a VUS in SLC7A3. We propose SLC7A3 as a likely candidate gene for epilepsy and/or developmental/cognitive delay and provide an overview of the 27 SLC genes related to epilepsy by other preclinical and/or clinical studies.
|Status||Udgivet - 1. feb. 2022|
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