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Prader-Willi Syndrome and Schaaf-Yang Syndrome: elucidation of molecular mechanisms

The genes of several brain-specific ncRNAs which were first identified by my group by Experimental RNomics, from the class of small nucleolar RNAs (snoRNAs) are located on chromosome 15q11-13 in humans (two of them, i.e SNORD115 and SNRD116, in multi-copy repeats). This region has been shown to be involved in the etiology to the Prader-Willi-Syndrome (PWS) a neuro-developmental disease. We could show that the brain-specific RNAs are not expressed in PWS patients pointing to a role of these RNAs in disease, which was later demonstrated by microdeletions in PWS patients lacking the SNORD116 gene cluster (ref). We are thus currently investigating the role of brain-specific non-messenger RNAs in the etiology of PWS by various molecular and cell biology approaches.

In addition to PWS snoRNAs, i.e SNORD115 and SNORD116, we also recently have focused on a protein coding gene within the PWS locus, designated as MAGEL2 protein. Frameshift mutations within this protein cause another neuro-developmental disease, the Schaaf-Yang Syndrome (SYS). Since PWS and SYS share many disease related features, such as…, we want to elucidate a potential connection between the PWS snoRNAs and MAGEL2 in the etiology of the two diseases.

The MAGEL2 and snoRNA genes on human chromosome 15q11.2-q13. Depicted is the imprinted PWS critical region on human chromosome 15q11.2-q13. The MAGEL2 gene is located upstream of the SNORD116 gene cluster and is indicated by the red star. The minimal critical region is marked by the yellow box. Adapted from Cavaillé [4].