Novel TTC19 mutation in a family with severe psychiatric manifestations and complex III deficiency

Célia Nogueira, José Barros, Maria José Sá, Luísa Azevedo, Ricardo Taipa, Alessandra Torraco, Maria Chiara Meschini, Daniela Verrigni, Claudia Nesti, Teresa Rizza, João Teixeira, Rosalba Carrozzo, Manuel Melo Pires, Laura Vilarinho, Filippo M. Santorelli

Research output: Contribution to journalArticlepeer-review


Complex III of the mitochondrial respiratory chain (CIII) catalyzes transfer of electrons from reduced coenzyme Q to cytochrome c. Low biochemical activity of CIII is not a frequent etiology in disorders of oxidative metabolism and is genetically heterogeneous. Recently, mutations in the human tetratricopeptide 19 gene (TTC19) have been involved in the etiology of CIII deficiency through impaired assembly of the holocomplex. We investigated a consanguineous Portuguese family where four siblings had reduced enzymatic activity of CIII in muscle and harbored a novel homozygous mutation in TTC19. The clinical phenotype in the four sibs was consistent with severe olivo-ponto-cerebellar atrophy, although their age at onset differed slightly. Interestingly, three patients also presented progressive psychosis. The mutation resulted in almost complete absence of TTC19 protein, defective assembly of CIII in muscle, and enhanced production of reactive oxygen species in cultured skin fibroblasts. Our findings add to the array of mutations in TTC19, corroborate the notion of genotype/phenotype variability in mitochondrial encephalomyopathies even within a single family, and indicate that psychiatric manifestations are a further presentation of low CIII.

Original languageEnglish
Pages (from-to)153-160
Number of pages8
Issue number2
Publication statusPublished - May 2013


  • Cerebellar ataxia
  • Complex III
  • Olivo-ponto-cerebellar atrophy
  • Psychiatric manifestations
  • TTC19

ASJC Scopus subject areas

  • Genetics(clinical)
  • Cellular and Molecular Neuroscience
  • Genetics


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