Successful Diagnosis of Sengers Syndrome Using a Comprehensive Genomic Analysis

Abstract

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.

Keywords

• genetic analysis
• mitochondrial disease
• mitochondrial DNA depletion syndrome
• mitochondrial respiratory chain complex deficiencies
• Sengers syndrome