Diagnostik- und Forschungszentrum

Research focus: Rare diseases

PI: Sarah Verheyen

Focus: The diagnosis of unclear rare diseases requires the use of different genetic testing methods. We aim to offer optimized diagnostics for our patients. In some cases, the examinations go beyond "routine diagnostics". In close cooperation with our colleagues of the neuropediatric outpatient clinic of the University Clinic for Pediatrics and Adolescent Medicine, Med Uni Graz, a systematic clinical characterization and different sequencing technologies are used to find the cause of genetic syndromes, developmental disorders and malformations. In cooperation with the Diagnostic and Research Institute of Pathology and the Vascular Outpatient Clinic of the Department of Pediatric Surgery, Med Uni Graz, we are working on improving the diagnostics for mosaic diseases.

To ensure the quality of the constantly evolving sequencing technologies and methods for data analysis, we collaborate with other Austrian human genetics institutes. Our projects in this area focus on the joint further development of diagnostic possibilities and quality standards.

Network: Within the Med Uni Graz we are part of a pediatric exom board: monthly case conferences, discussion of diagnostic procedures, discussion of findings and planning of scientific clarification of selected cases (Cooperation with the University Clinic for Pediatrics and Adolescent Medicine). Furthermore, we participate in Austrian exome meetings (Cooperation with Human Genetics Institutes in Vienna (Meduni Vienna, Hanusch Hospital), Salzburg, Innsbruck and Linz). For single case-related projects, we have worldwide cooperations with different laboratories/scientists.



  • "Mosaic diseases" arise from somatic mutations during embryogenesis or later in life. The resulting phenotype of a somatic mutation depends on the number and organization of mutation-bearing cells, the effect of the mutation on cell function, and the distribution of these cells the body. If the mutation affects pathways that regulate cell growth, apoptosis, or cell migration, regional changes in tissue (e.g. tissue hypertrophy or an increased risk for cancer) may occur as consequence. Many mosaic diseases are caused by mutations in the PIK3CA / PTEN / AKT / TSC / mTOR pathway (e.g. Proteus syndrome, CLOVES syndrome, PROS, MCAP). Detection of "low grade" mosaics is only possible by direct examination of affected tissue in many cases and requires high-resolution sequencing technologies that are not used in routine diagnostics. However, biopsy of affected tissue is not possible in all cases due to patient burden. The aim of the project is the improvement and evaluation of diagnostic applications. Resolution limits of different methods, the genotype-phenotype correlation (with histopathological assessment of the examined tissues), the variant allele frequency in different tissue samples of a patient (such as blood, skin biopsy, cell-free DNA (cfDNA), urine) are assessed. We aim to identify novel causative genes, driver mutations and pathways by comparative exome analyses (affected vs. unaffected tissue).
  • Duration: since 2018
  • Funded by: Med Uni Graz
  • Project partners: Diagnostic and Research Institute for Pathology, University Clinic for Pediatric Surgery, University Clinic for Pediatrics and Adolescent Medicine, Med Uni Graz

Austrian Exome Meeting

  • The Austrian Exome Meeting is an event initiated and coordinated by our research team that takes place 3 times/year. The main goal is to further develop our diagnostic methods for clarification of rare diseases using Next Generation Sequencing technologies. Unsolved cases or cases with causal variants for which the detection or interpretation is challenging, are exchanged among the participating institutions for comparative analysis. Objectives: Establishment of common quality standards, continuing education through expert lectures, development of an Austria-wide infrastructure for a more uniform  variant interpretation (variant database).
  • Duration: since 2018
  • Funded by: Med Uni Graz
  • Project partners: Institute of Medical Genetics, Med Uni Vienna, Institute of Human Genetics, Med Uni Innsbruck, Unit for Clinical Genetics, University Hospital Salzburg of the PMU, Center for Medical Genetics Vienna, Hanusch Hospital, Laboratory for Molecular Genetic Diagnostics, Ordensklinikum Linz


Diagnostic and Research Institute of Human Genetics

Sarah Verheyen  
T: +43 316 385 73816