Schoonen 2015 Abstract MiPschool Cape Town 2015
|Nuclear gene variants associated with complex I of the respiratory chain in Southern African children diagnosed with RCDs.|
Event: MiPschool Cape Town 2015
Information to better understand the aetiology of mitochondrial disease in African populations is still lacking to a great extent. Disease diagnosis is mostly based on criteria and information from other populations and is compounded by issues such as lack of awareness and inadequate diagnostic procedures at the major academic medical institutions. In a South African paediatric patient cohort of ~200 cases with a predominantly muscle phenotype we have previously found a very low prevalence of common and other mtDNA mutations. Complex I-associated nuclear gene mutations were investigated using a targeted enrichment sequencing approach. For this study, 32 patients, diagnosed with a CI deficiency, were included. Target enrichment of 92 CI-associated nuclear genes (coding sequences) was done using Agilents Haloplex target enrichment system and next-generation sequencing by an Ion Torrent PGM. Data analysis was done using an in-house bioinformatics pipeline. Following data analysis and validation of CI nuclear genes, an average of 750 variants were identified. Of these variants an average of 5 novel variants and 4 variants classified as possibly pathogenic were identified per patient. These variants are of interest for further evaluation. As these variants have varied potential to be disease-causing, and thus would require further investigation, we give here an overview of these variants and key parameters for an initial estimation of pathogenicity. At this time we successfully sequenced and evaluated CI nuclear genes and can conclude that, as is the case for mtDNA, there is a general lack of known mutations that cause complex I deficiency in African patients. The pathogenicity of novel variants and interactions between variants remain to be further evaluated to better understand the genetic basis of the disease in this population.
Labels: MiParea: mtDNA;mt-genetics, mt-Medicine, Patients, mt-Awareness
Enzyme: Complex I
North-West Univ, South Africa. - [email protected]