Analysis of mitochondrial DNA copy number variation in cases of mitochondrial disorders in accordance to the respective type of mutation

• Grant number: 14/05076-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2014
• End date: March 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Suely Kazue Nagahashi Marie
• Grantee: Carlos André Oshiro
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine, AP.TEM

Abstract

The mitochondrial diseases comprise a heterogeneous group of diseases characterized by the mitochondrial respiratory chain dysfunction, leading mainly neurological and muscular deffects. Depletion of mtDNA copy number is already characterized as a heterogeneous class of diseases nominated MtDNA depletion syndromes and its impact on cellular physiology is also a target of studies. This research project aims to investigate three types of mtDNA mutations associated to: Leigh Syndrome, MELAS, MERRF, Infantile reversible cyctochrome oxidase deficiency myopathy, CPEO and KSS. The mutation profile will be analyzed in relation to the number of copies of mtDNA in skeletal muscle and peripheral blood, and also to the severity of the phenotype and histo-histochemical alterations. Sixty-nine samples with clinical diagnosis of mitochondrial diseases will be studied by molecular approach by long PCR, conventional PCR and real-time PCR, in addition to the analysis of clinical findings and microscopic examination of muscle biopsies stained for HE, Gomori, SDH and COX. It is expected to analyze the correlation among the type of mutation, the variation of mtDNA copy number and the disease phenotype, in order to contribute to further diagnostic methods and therapeutic approaches.