Molecular Genetic Findings in Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is caused by the loss of paternal gene expression from an imprinted region on chromosome 15q11.2-q13.1, usually from a deletion of the 15q11-q13 region involving proximal chromosome 15q11-q13 breakpoints BP1 or BP2 and distal breakpoint BP3. Here, we review the structure, function and imprinting status of both protein coding and non-coding genes in the extended chromosome 15 region from BP1-BP5. The region is characterized by complex genomic imprinting, that includes both maternal, paternal and non-imprinted genes. PWS was the first genetic disorder found to be due to errors in genomic imprinting in humans. The protein coding genes of this region have diverse functions, such as magnesium transport and protein ubiquitination, pigment production, and are part of splicing components and neurotransmitter receptors. The non-protein coding genes act in imprinting or regulation of distant gene regions and influence pre-mRNA processing, but most of their functions are still elusive. Unlike Angelman syndrome, a sister genomic imprinting disorder due to loss of function of the maternally expressed UBE3A gene found in the same chromosome 15 region, not a single gene stands out as the sole contributor to PWS which has to be taken into account for all therapeutic interventions.