GENOMIT has already created a genomic database involving of more than 2,000 patients with suspected mitochondrial disorders. A molecular diagnosis was found in about 50 % of these patients investigated by whole exome or whole genome sequencing (WES, WGS).
Despite the diagnostic power of WES/WGS analysis the molecular cause of about half of cases will not be resolved by DNA-sequencing demanding the integration of further molecular tools in the diagnostic process.
In this context we will use RNA-sequencing as a powerful tool to identify aberrant splicing, expression outliers and monoallelic expression, which is expected to provide a gain in diagnostic yield of 10-20%. However, a significant proportion of pathogenic alterations can be seen neither by DNA- nor by the RNA-sequencing but may affect protein folding and stability. These alterations can be identified by proteomics techniques, which will be used as complementary screening methods in this study.
This subproject is coordinated by Klinikum rechts der Isar (IHG TUM-MED, Munich), in cooperation with partners Salzburger Landeskliniken (SALK), Institute Imagine (INSERM, Paris), Friedrich-Bauer-Institute (LMU Munich) University of Pisa, Chiba Children´s Hospital (CCH, Chiban, Japan) and Newcastle University (WCMR)