Instabilidade do DNA mitocondrial na oftalmoplegia externa crônica progressiva: estudo familial

Abstract

Objective: To identify genetic changes in mitochondrial DNA (mtDNA) and genotypes of GSTM1 and GSTT1 genes in patients with progressive chronic external ophthalmology (OECP). A total of 27 family volunteers consisting of five OECP patients participated in the study. Alterations in mtDNA were investigated by gene sequencing methodology and genotypes for GSTs by multiplex-PCR. A total of nine mutations have been demonstrated, and none have been described in the current literature. We understand that further studies may relate them to OECP disease. GSTM1 null genotype was found in 16 individuals (53.3%), 14 family members and two patients. GSTT1 null genotype was found in only one individual. The OECP patient with normal GSTM1 has a less severe clinic than those with null GSTM1. We believe that the presence of null GSTM1 directly influences the ability of isoenzymes to reduce oxidative stress in these patients, being a risk factor for the severity and symptoms and early onset of the disease. All mutations found were in heterozygosis, which was expected due to the heteroplasmy normally present in these individuals. Based on our results, we concluded that the present study and mainly the large sample (30 family members) contributed to confirm new OECP-related mutations and especially early establishment of genetic factors that could improve the monitoring and treatment of patients with Myopathy. mitochondrial disease, besides contributing to the establishment of specific subphenotypes of this disease. It is noteworthy that this was the first study in the literature that discusses the probable correlation of GST genotypes with clinical severity in patients diagnosed with mitochondrial OECP disease

Keywords: Mitochondrial Disease, Myopathy, Ophthalmoplegia, Genotype, Phenotype, Polymorphism.