A Case Report: Identification of a Pathogenic Microdeletion at Chromosome 21q21.3q22.13 Using Whole-Exome Sequencing...

Copy number variations (CNVs) affecting the chromosomal region 21q21.3-q22.13 are rare and have been increasingly associated with neurodevelopmental abnormalities and multisystemic manifestations. In this study, we aimed to characterize the clinical, genomic, and genotype-phenotype correlations of a Moroccan child carrying a de novo microdeletion in this region. Whole exome sequencing (WES) was performed using sequencing-by-synthesis technology on the GenoLab M platform, and CNV detection was achieved through the SeqOne platform. Variant interpretation was conducted using the Integrative Genomics Viewer (IGV), and a custom gene-phenotype heatmap was generated in R (ComplexHeatmap and pheatmap) based on OMIM, ClinVar, and DECIPHER databases to prioritize candidate genes within the deleted segment. The patient presented with global developmental delay, microcephaly, psychomotor and staturo-ponderal retardation, facial dysmorphism, epilepsy responsive to treatment, and cerebral anomalies, including passive biventricular hydrocephalus and diffuse cortical atrophy. WES-CNV analysis identified a heterozygous de novo microdeletion of approximately 8.2 Mb in 21q21.3-q22.13, encompassing 124 clinically relevant genes. Integrated analysis confirmed the pathogenicity of the deletion and highlighted genotype-phenotype correlations, particularly implicating dosage-sensitive genes such as SON and RUNX1. This case underlines the clinical utility of combining WES, CNV analysis, and phenotype-based bioinformatic tools for diagnosing complex microdeletion syndromes, contributes to understanding genotype-phenotype relationships in 21q21.3-q22.13 deletions, and supports improved clinical interpretation and patient management.