Dissecting Down Syndrome * Study on the Variability in Phenotype

Down syndrome (DS) is the most frequent genetic cause of intellectual
disability. DS is explained by the presence of an additional chromosome 21
which serves as the basis of DS-pathogenesis. However, underlying cellular and
molecular processes causing the DS-phenotype remain not well understood. Also,
among DS individuals a wide variability of phenotypic features can be observed
which can not be explained yet.

Several hypotheses exist regarding the implications and effects of the presence
of an extra copy of chromosome 21. A disturbed methylation by the presence of
an additional copy of chromosome 21 has not been explored to date. The location
of chromosomes within the nucleus has become known to be important in the
methylation process. Altered methylation may influence transcription of genes
located on chromosome 21 and also genes elsewhere in the genome.

We aim to obtain more insight in the pathogenesis of DS and the potential role
of methylation in this by a small initial study (proof of principle). If the
study shows a potential role of disturbed methylation in DS pathogenesis we
will subsequently initiate a similar study in a large cohort.

Observational study (proof of principle) with invasive measurements.

The samples will be obtained when blood sampling is needed because of clinical
care. For the control indivduals the samples will be obtained from the general
lab anonymously ('restmateriaal').