Karolinska Undiagnosed Diseases Program (K-UDP) clinical site is located at Karolinska University laboratory where the Dep of Clinical genetics, is the clinical coordinating center, and Genomic Medicine Center Karolinska (GMCK), in collaboration with SciLifeLab, the sequencing core. The Rare Diseases research group is part of the Undiagnosed Diseases Network International (UDNI) - an international collaboration with research sites worldwide that work with the purpose to bring together clinical and research experts from across the world to solve the most challenging medical mysteries using advanced technologies. The UDP concept requires international collaboration and multidisciplinary one-stop shop outpatient clinics for diagnostics of patients with rare diseases of all ages.
The rare diseases group takes part in two European Reference Networks (ERNs): ITHACA (congenital malformations and rare intellectual disability) and BOND (Rare Bone Disorders) as well as Solve-RD – A H2020 funded five-year project that aims to identify diagnosis in unsolved patients.
We follow up on patients that are still undiagnosed after routine clinical evaluation and use bioinformatic reanalysis of whole genome sequencing (WGS) data where we also perform structural variant analysis (developed in house, see below) as well as other multi-omics approaches including RNA sequencing. We also participate in international projects where pooling of cases increases the chances of identifying causal variants. Functional evaluation of new candidate disease genes is performed in our own lab, in collaboration with the Metabolomics core at CMMS or other research groups working with model organisms at KI, within UDNI, ERN or at other centers. First, we evaluate effects on expression and splicing patient cell lines using RT-PCR, qPCR and Western blotting.
Specific research projects are:
1. Gene discoveries and identification of novel mutational mechanisms
2. Cancer predisposition syndromes and familial childhood cancers
3. The role of structural genomic variation in human health and disease
4. Cognition, Behavior and Pedagogical strategies in Individuals with genetically defined subgroups of Neurodevelopmental syndromes