Abstract
BACKGROUND: Sengers syndrome is an autosomal recessive mitochondrial DNA depletion syndrome characterized by hypertrophic cardiomyopathy, congenital cataracts, skeletal myopathy, exercise intolerance, and lactic acidosis. Dysfunction of acylglycerol kinase (AGK) is responsible for the disease, and several AGK gene variants have been reported. METHODS: We employed a comprehensive genomic analysis approach, including whole-genome sequencing and RNA sequencing, combined with various bioinformatics tools. RESULTS: Our analysis successfully diagnosed Sengers syndrome in a patient by detecting a known pathogenic variant and a previously unreported large deletion involving the AGK gene in a segmental duplication. CONCLUSION: This study demonstrates the effectiveness of combining multiple genomic analysis approaches for the accurate diagnosis of Sengers syndrome, particularly in cases involving complex genetic variations such as large deletions in segmental duplications.