Deciphering the etiology of genetic diseases is not only important for affected patients and their families but also for the advancement of medicine in general. Knowledge of the molecular defect allows an etiological diagnosis in clinically complex and heterogeneous disorders which then allows better clinical management. Furthermore, understanding of molecular pathomechanisms is essential for development of future therapeutic interventions.
Today thousands of Mendelian traits have been clinically described. Although most of these traits are individually rather rare, as a sum their contribution is sizable and current estimates suggest that more than 5% of the population is affected by such disorders. Establishing a diagnosis of a Mendelian disorder, though, is often hampered either because the underlying disease gene has in general not yet been identified or because effective diagnostic tools are lacking in clinically and genetically heterogeneous conditions. Concerning the primary identification of novel disease genes, the new genetic strategies based on “next generation sequencing” have mainly superseded the classical positional cloning strategies of the past and have allowed identification of genetic defects not only in the limited number of more frequent monogenic conditions but also in genetically very heterogeneous common disorders such as intellectual disability, where clinical classification often is not possible. Due to the unforeseen clinical and genetic variability of many Mendelian disorders, next generation sequencing was also proven to significantly increase diagnostic yield for well-established genes. Finally, even if a diagnosis can be established, our current knowledge about genotype-phenotype correlation and natural history is limited for many rare genetic disorders.
The IMG’s perception of research is therefore to systematically unravel the genetic cause and molecular mechanisms of genetic disorders, to investigate genotype-phenotype correlation, natural history and potential therapeutic targets and finally to improve diagnostics and management of genetic disorders. Keywords characterizing this approach of Medical Genetics are basic and translational research, research on health care provision, rare diseases and personalized medicine.