Prader-Willi Syndrome
The Genetics
Contact Details
*   *

Chromosome 15 contains an ‘Imprinted Region’. This means that normally the paternally contributed region of chromosome 15 is expressed whilst the maternal contribution remains inactive. Consequently an individual must receive a normal paternal imprinted region on chromosome 15 as the inactive maternal copy will not compensate for its loss.

The imprinting of these genes seems to be under the control of the Imprinting Centre (IC) which maps between the loci D15S63 and SNRPN loci. [Dittrich 1992, Nicholls 2000]

A mutation in the IC can appear suddenly in which case the individual expresses maternal IC on both chromosomes as represented in the diagram below. Consequently there is no active paternal IC, the individual has two inactive regions and therefore will develop PWS.

(M=maternal chromosome P=paternal chromosome)

On occasion an IC defect can be inherited as follows. Normally when imprinted region genes are passed down the imprints are cleared and new imprints are made, according to the sex of the parent. However if a male transmits a maternal imprinting mutation from his own mother, the maternal epigenotype is not erased as the mutation blocks the maternal-paternal switch which would normally occur. Consequently maternal imprinting is passed onto half of the man’s gametes and any individual who inherits this abnormal epigenotype will lack the paternal contribution and present with PWS. Click here to view a diagram of the Inheritance of an IC Mutation.

Importantly IC mutations have no direct effect on the carrier as they still possess the paternal IC region. Carriers are at risk of passing it onto their children as the mutation only manifests itself when it is passed through to the opposite sex by gametogenesis.

Buiting et al  studied three such cases of PWS where the individual had abnormal DNA methylation at several loci within 15q11-13 which implied a defect in the IC. [Buiting 1995] In these cases, a deletion was infact located in the IC of the paternal chromosome of the patients and also on the maternal chromosome of the phenotypically normal fathers. The paternal grandmother of two of the three families also had the deletion on their maternal chromosome. The patients had essentially inherited an imprinting mutation from their father, who had inherited the mutation from his mother.

< Back

*   *
*   *

© Sally Price 2007  Leeds