Genomic Characterization of Pathogenic CNVs in a Familial Developmental Dyslexia Comorbid ADHD: A Case Study from Pakistan

Background Developmental dyslexia (DD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur and are believed to share genetic risk factors. However, genomic evidence from South Asian populations remains limited, restricting insight into population-specific variants. Methodology: An integrated clinical, biochemical, and genomic investigation was conducted in a Pakistani family, focusing on a 9-year-old female proband diagnosed with comorbid DD and ADHD. Neuropsychological assessments evaluated reading ability, attention, and executive function. Biochemical profiling assessed neurotransmitter levels, vitamin D status, fatty acid composition, and oxidative stress markers. High-resolution Cytoscan HD microarray analysis was performed, followed by qPCR validation and familial segregation analysis. Results Neuropsychological testing revealed significant deficits in reading, attention, and executive functioning. Biochemical analysis demonstrated neurotransmitter dysregulation, vitamin D insufficiency, fatty acid imbalance, and elevated oxidative stress. Microarray analysis identified a heterozygous 258 kb de novo deletion at chromosome 17q12 (chr17:34.82–35.08 Mb; hg38), encompassing six genes involved in neurodevelopment and neuronal signaling. qPCR confirmed the deletion exclusively in the proband. Based on ACMG criteria, the copy number variant was classified as likely pathogenic. Discussion The findings suggest that rare structural variants may contribute to the comorbid presentation of DD and ADHD, potentially interacting with metabolic abnormalities to influence disease expression. Conclusion This study highlights the importance of CNV screening and integrative genomic approaches in underrepresented populations to improve understanding and diagnosis of neurodevelopmental disorders.