Rare and ultra-rare diseases affect less than 1 in 2000 and 1 in 50,000 people, respectively, and the majority have a genetic cause. Even though these diseases are individually rare, there are >300 million rare disease patients globally. Whole Genome Sequencing (WGS) has revolutionized the diagnostic routines in these patients, but still more than 50% of the patients analyzed remain without a molecular diagnosis.
We study patients with congenital neurological disorders where diagnostic WGS did not provide a molecular diagnosis. While diagnostic analyses are typically restricted to documented morbid genes, we extend our analyses to all human genes, facilitating the identification of novel disease genes (i.e. genes not yet known to cause human diseases when mutated).
We analyze WGS- and RNA-sequencing (RNA-seq) data from the patients. RNA-seq provides a powerful complementary tool for identifying disease-causing mechanisms through the detection of abnormal gene expression (OUTRIDER) and aberrant splicing (FRASER). These approaches facilitate the detection of coding and non-coding disease-causing variants, provide functional evidence of pathogenicity and molecular mechanisms that may be missed by DNA-based analyses alone, thus improving diagnostic yield.
Findings are shared through Genematcher.org to identify unrelated patients with pathogenic variants affecting the same gene presenting with overlapping phenotypes. We further explore the functional consequences of putative pathogenic variants by in vitro and in vivo modelling.
Our project reveals unique knowledge about the etiology of congenital neurological disorders, which is crucial knowledge for the development of future therapy.
The research group is a part of Institute of Clinical Medicine, University of Oslo, and the Research section at the Department of Medical Genetics, Oslo University Hospital.
Read more about our research on our website at Oslo University hospital
Research projects
Molecular characterization of encephalopathies with childhood onset
Severe encephalopathies of likely genetic origin are clinically heterogeneous with life-long morbidity. These diseases can be caused by pathogenic variants in genes involved in a wide range of cell physiological processes.
Our research the last >10 years has identified the disease-causing variant in about two-thirds of the families analyzed and documented the molecular cause of several novel disease entities.
Read more about the project on our website at Oslo University hospital.
Novel genes causing primary cilia dysfunction in congenital brain malformations
A primary cilium protrudes from the plasma membrane on nearly all cells in the human body where it senses the external environment and triggers appropriate cell responses. The primary cilium is necessary for a wide range of physiological processes already during embryonic life.
Our project characterizes the molecular basis of congenital brain anomalies caused by primary cilia dysfunction. We recruit patients who lack a molecular diagnosis after WGS-based diagnostic analyses.
Read more about the project on our website at Oslo University hospital.
Combined genomics and transcriptomics in rare neurometabolic disease research
We recently initiated a project to identify and characterize the disease etiology in patients with clinical symptoms of neurotransmitter disease. These disorders present predominantly with neurological features, including dystonic or dyskinetic cerebral palsy and movement disorders in general.
Read more about the project on our website at Oslo University hospital.
Externally Funded Projects
Our research projects have received funding from the Norwegian National Advisory Unit on Rare Disorders. We have also received funding for PhD-students through The Research Council of Norway's Quota scheme.
