Molecular characterization of severe progressive encephalopathies in childhood
Progressive encephalopathies (PE) in children are clinically and genetically heterogeneous. Affected individuals usually exhibit developmental arrest before regression, and cerebral MRI show loss of neural tissue or abnormal signaling intensity.
Our aim is to identify disease-causing genetic variants in undiagnosed PE and to perform functional analyses in novel disease genes.
In this project we have so far included >80 patients from 60 families negative for known lysosomal, mitochondrial, peroxisomal, and amino- and organic acid, and other relevant metabolic and degenerative diseases with no history of infectious diseases or perinatal hypoxia.
We perform Whole Exome Sequencing (WES) in family trios (one child and parents) or inverted trios (two children and one parent) and continue with data filtering (population frequency, estimated severity of variants, inheritance pattern). We also perform Whole Genome Sequencing (WGS) on selected families where we have not detected clinically relevant WES results.
Hypotheses about the molecular consequences of the genetic variants detected are explored in in vitro experiments in cell lines mostly established from the patients.
WES and WGS are performed at the Norwegian High-Throughput Sequencing Centre, NSC.
Read more about our project on ous-research.no