PhD Scientific Days 2022

Neurosciences I. (Poster discussion will take place in the Aula during the Coffee Break)

The importance of the mtDNA 13513 G>A mutation - a case study of five patients from Hungary

Text of the abstract

Introduction: Mitochondrial DNA's pathogenic mutations can manifest in a group of quite complex disorders called primary mitochondrial diseases, with multisystemic involvement. The m.13513 G>A (p.D355N) mutation in the MT-ND5 gene is associated with different clinical outcome and can manifest as Leigh syndrome, MELAS, and MELAS/LHON overlap syndrome.

Aims: In our study, we analyzed how specifically frequent this mtDNA mutation is in the Hungarian population.

Method: We examined 537 patients for the m.13513 G>A mutation by bidirectional
sequencing (also called the Sanger method). 390 DNA isolations were performed from blood sample and 147 from postmitotic tissue sample (muscle, urinary squamous cell).

Results: We could detect the mtDNA G13513A mutation in five cases from the 537 patients. The heteroplasmy ratio turned out to be between 50 and 95%. The clinical symptoms of the 5 examined patient who carries this alteration, showed a broad spectrum of
phenotypes such as Leigh syndrome, ataxia, strabismus, neuropathy, visual impairment, and renal failure. In four cases, the disease was associated with early onset Leigh syndrome, while in one patient, clinical symptoms manifested in adulthood with multisystemic involvement, with severe visual and renal impairment and hypoacusis.

Conclusion: Approximately 1% of the total investigated cohort carried the m.13513 G>A mtDNA mutation. Interestingly, among the postmitotic tissues samples, this proportion was significantly higher (2.88%). As a consequence, a more comprehensive study of the m.13513 G>A mutation is important to perform not only from blood sample but also from postmitotic tissue as well.

Funding: Hungarian Brain Research Program, NKFIH_FK_132812, NKFIH_139010, Semmelweis University, Startup grants, János Bolyai Research Scholarship, UNKP-21-5 Research Scholarship