Leigh Syndrome Due to mtDNA Pathogenic Variants

Cristina Pereira, Carolina Fischinger de Souza, Leonardo Vedolin, Filippo Vairo, Cláudia Lorea, Cláudia Sobreira, Célia Nogueira, Laura Vilarinho

Research output: Contribution to journalArticlepeer-review


Leigh syndrome is a devastating neurodegenerative disease, typically manifesting in infancy or early childhood. Hallmarks of the disease are symmetrical lesions in the basal ganglia or brain stem on MRI, and a clinical course with rapid deterioration of cognitive and motor functions. It is genetically heterogeneous, causative mutations have been disclosed in mitochondrial DNA and nuclear genes involved in the process of energy production in the mitochondria. We investigated the whole mitochondrial DNA in three Brazilian patients with LS, based on their clinical and biochemical data, with the aim to identify the disease-causing mutations. In two of the patients, with complex I deficiency, a novel heteroplasmic variant m.4142G>T (p.R279L) in MT-ND1 and a recurrent homoplasmic mutation m.10197G>A (p.A47T) in MT-ND3 were identified. In the remaining patient, with complex IV deficiency, a de novo heteroplasmic variant in MT-CO1 m.6547T>C (p.L215P) was found. The molecular investigation in mitochondrial diseases have shifted their focus from mitochondrial DNA to nuclear DNA, however, mtDNA protein-coding genes are one of the important genetic causes of mitochondrial disorders for Leigh syndrome. This study expands the molecular and clinical spectrum associated with this disease.

Original languageEnglish (US)
Article numbere20180003
JournalJournal of Inborn Errors of Metabolism and Screening
StatePublished - 2019


  • MT-CO1
  • MT-ND3
  • complex I
  • complex IV
  • leigh syndrome
  • mitochondrial genome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Genetics(clinical)


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