Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3

Esther Leshinsky-Silver*, Dorit Lev, Gustavo Malinger, Daniel Shapira, Sarit Cohen, Tally Lerman-Sagie, Ann Saada

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Leigh syndrome can be caused by defects in both nuclear and mitochondrial genes involved in energy metabolism. Recently, an increasing number of mutations in mitochondrial DNA encoding regions, especially in NADH dehydrogenase (respiratory chain complex I) subunits, have been reported as causative of early onset Leigh syndrome. We describe a patient whose fetal brain ultrasound demonstrated periventricular pseudocyst suggestive of a possible mitochondrial disorder who presented postnatally with Leigh syndrome. A muscle biopsy demonstrated a partial decrease in complex I and pyruvate dehydrogenase (PDH-E1α) activity. Sequencing of the PDH-E1 alpha gene did not reveal any mutation. Sequencing of the mtDNA revealed a novel heteroplasmic G10254A (D66N) mutation in the ND3 gene. This change results in a substitution of aspartic acid to asparagine in a highly conserved domain of the ND3 subunit. The mutation could not be detected in the mother's blood or urine sediment. Blue native gel electrophoresis of muscle mitochondria revealed a normal size, albeit a decreased level of complex I. The G10254A substitution in the mtDNA-ND3 gene is another cause of maternally inherited Leigh syndrome. This case demonstrates that periventricular pseudocysts may be the initial in utero presentation in patients with mitochondrial disorders. We emphasize the importance of screening the mtDNA in pediatric patients as the first step in molecular diagnosis of Leigh syndrome.

Original languageEnglish
Pages (from-to)65-70
Number of pages6
JournalMolecular Genetics and Metabolism
Volume100
Issue number1
DOIs
StatePublished - May 2010
Externally publishedYes

Keywords

  • Leigh syndrome
  • Mitochondria
  • ND3
  • Respiratory chain
  • mtDNA

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