MITOCHONDRIAL MYOPATHY CAUSED BY MT-ND5 VARIANT: INTEGRATING WES AND MITOCHONDRIAL DNA ANALYSIS

Abstract

Mitochondrial disorders caused by pathogenic variants in mitochondrial genome represent a heterogeneous group of disorders, including mitochondrial myopathy, Leigh syndrome, MELAS and others. We report a patient with mitochondrial myopathy caused by a pathogenic variant in the MT-ND5 gene. The patient is a male child born after an uneventful full-term pregnancy from healthy nonconsanguineous parents. He presented with failure to thrive with psychomotor delay and recurrent infections. Neurologic examination at 11 months revealed axial hypotonia with limb hypertonia, hyperreflexia, head tremor, weak supporting and postural responses, hypomimic face, bilateral eyelid semiptosis, convergent strabismus and inability to visually track objects. Elevated serum lactate prompted further metabolic analyses which indicated a defect in oxidative phosphorylation. Whole exome sequencing (WES) analysis aimed at nuclear-encoded mitochondrial genes was negative, but the analysis of mitochondrial DNA revealed a pathogenic variant c.758T>C (p.Val253Ala) in the MT-ND5 gene, with a heteroplasmy level of 54%. Variant was confirmed by Sanger sequencing, while the analysis of maternal sample showed that the variant arose de novo. This study highlights the importance of integrating mitochondrial DNA analysis with WES to enable precise diagnosis and treatment of different mitochondrial disorders.Book of abstract: 15th Balkan congress of human genetics and 3rd Alpe Adria meeting of human genetics, 9 - 11 October 2025, Rikli Balance Hotel ,Bled, Sloveni