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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Celia Nogueira (Autor) Outra; Jose Barros (Autor) ICBAS; Maria Jose Sa (Autor) Outra; Luisa Azevedo (Autor) FCUP; Ricardo Taipa (Autor) Outra; Alessandra Torraco (Autor) Outra; Maria Chiara Meschini (Autor) Outra; Daniela Verrigni (Autor) Outra; Claudia Nesti (Autor) Outra; Teresa Rizza (Autor) Outra; Joao Teixeira (Autor) Outra; Rosalba Carrozzo (Autor) Outra; Manuel Melo Pires (Autor) ICBAS; Laura Vilarinho (Autor) Outra; Filippo M Santorelli (Autor) Outra

Revista

Título: Neurogenetics

Vol. 14

Páginas: 153-160

ISSN: 1364-6745

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 21 Citações

Scopus - 30 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

Outras Informações

ID Authenticus: P-005-120

DOI: 10.1007/s10048-013-0361-1

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica