Investigation of tRNALeu/Lys and ATPase 6 Genes Mutations in Huntington’s Disease

Abstract

Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats which code for glutamine in the HD gene product, huntingtin. Huntingtin is expressed in almost all tissues, so abnormalities outside the brain can also be expected. Involvement of nuclei and mitochondria in HD pathophysiology has been suggested. In fact mitochondrial dysfunction is reported in brains of patients suffering from HD. The tRNA gene mutations are one of hot spots that can cause mitochondrial disorders. In this study, possible mitochondrial DNA (mtDNA) damage was evaluated by screening for mutations in the tRNA(leu/lys) and ATPase 6 genes of 20 patients with HD, using PCR and automated DNA sequencing. Mutations including an A8656G mutation in one patient were observed, which may be causal to the disease. Understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could potentially be important for the development of therapeutic strategies in HD.

Mitochondrial DNA Variants and Common Diseases: A Mathematical Model for the Diversity of Age-Related mtDNA Mutations

“…Regarding variants in mtDNA genes, Kasraie et al screened tRNALeu/Lys and ATPase 6 mutations in 20 Iranian HD patients. One patient showed the A8656G mutation in ATPase 6 (which induces a significant change in protein structure), resulting in defects in ATP production [68].…”

Consequences of Mitochondrial Dysfunction in Huntington's Disease and Protection via Phosphorylation Pathways

“…Despite unchanged activity of mitochondrial complexes, this cell model presented evidences of mitochondrial dysfunction based on significant changes on mitochondrial membrane potential and increased ROS generation (Ferreira et al 2010). The presence of mtDNA variations, including an 8656A N G variant in one patient, was previously shown in a screening study for mutations in the tRNA(leu/lys) and MTATP6 genes of 20 patients with HD (Kasraie et al 2008). However, the nucleotides 8915-9207 of the same gene did not present any sequence variation in our HD cybrids (Ferreira et al 2010).…”

Investigation of tRNA Lys/Leu and ATPase 6/8 gene mutations in Iranian ataxia telangiectasia patients

“…All the patients were clinically defined as having AT by a neurologist according to generally accepted diagnosis criteria of AT [10]; all of the patients had gait ataxia, oculocutaneous telangiectasias, apraxia of eye movement or immunological defects that include immunoglobulin deficiencies (particularly IgA and IgE), high serum a-fetoprotein concentration and lymphopenia. If the diagnosis was uncertain, molecular genetic tests for ATM mutations were performed to confirm the diagnosis [2].…”