Whole Exome Sequencing in Patients With Developmental Delay/Intellectual Disability (DD/ID), Epilepsy and the First...

Whole-exome sequencing (WES) is considered an important tool in investigating the etiology of developmental delay/intellectual disability (DD/ID) and epilepsy. Genetic diagnosis with WES has become an important tool in patients with DD/ID and epilepsy.

In this study, we present the findings of WES conducted between August 2021 and December 2024 on children with DD/ID and epilepsy. We evaluated clinically important variants identified by WES in 65 pediatric patients by retrospective analysis.

Sixty-five patients with DD/ID were included in the study, 34 of whom (52.3%) were male. The most common symptom was epilepsy (45 patients, 69.2%), and the second most common symptom was DD/ID in 39 patients (60%). A total of 19 pathogenic/likely pathogenic variants (31.2%) with confirmation made in the parents and probands, 9 variants were determined to be de novo. In this study, the number of patients diagnosed was determined as 19 (31.2%). We detected a de novo likely pathogenic heterozygous c.142 T>C (p.Cys48Arg) variant in the BCL11A gene in the first reported Turkish patient with BCL11A-related intellectual disability. Other previously unreported de novo variants identified: ASXL3 gene, NM_030632.2 c.3613G>T p.(Glu1205Ter), ANKRD11 gene, NM_001256182.2 c.4750G>T, SHANK3 gene, NM_001372044.2 c.4711_4712del.

The cases we present contribute to the expansion of the spectrum of genetic variants in genetically heterogeneous patient groups such as DD/ID and epilepsy. These previously unreported variants advance our molecular understanding and broaden the clinical spectrum of these rare genetic disorders.