Objectives: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two syndromes that are caused by the same chromosomal deletion on 15q11.2-q13. Due to methylation patterns, different genes are responsible for the two distinct phenotypes resulting in the disorders. Patients of both disorders exhibit hypotonia in neonatal stage, delay in development and hypopigmentation. Typical features for PWS include hyperphagia, which leads to obesity, the major cause of mortality, and hypogonadism. In AS, patients suffer from a more severe developmental delay, they have a distinctive behaviour that is often described as unnaturally happy, and a tendency for epileptic seizures. For both syndromes, we identified and visualised molecular downstream pathways of the deleted genes that could give insight on the development of the clinical features.Methods: This was done by consulting literature, genome browsers and pathway databases to identify molecular interactions and to construct downstream pathways.Results: A pathway visualisation was created and uploaded to the open pathway database WikiPathways covering all molecular pathways that were found.Conclusions: The visualisation of the downstream pathways of PWS- and AS-deleted genes shows that some of the typical symptoms are caused by multiple genes and reveals critical gaps in the current knowledge.
Keywords: Rare diseases; behavioural phenotype; bioinformatics; neurological disorder; pathway analysis.