Rare diseases are defined as disorders that affect less than 1 in 2,000 individuals in the general population. However, collectively they affect more than 300 million people worldwide. It is estimated that there are approximately 7000 rare diseases of which 80% is thought to have a molecular cause. Notwithstanding that the implementation of whole exome sequencing in the clinic has rapidly increased the diagnostic yield in patients with rare disorders, the number of patients without a (molecular) diagnosis remains high. Presumably, the causal DNA defect is located outside the coding repertoire of the cell and it can be anticipated that for many of these patients, noncoding mutations or rearrangements in regulatory elements might be responsible for the observed phenotype. In this project we will hunt for the hidden variation associated with rare disorders. To this end, we will make use of (epi)genomics, transcriptomics, proteomics and state-of-the-art functional assays.