Deletion vs. UPD: 70/30 or 50/50?

Most information about PWS starts out with a brief overview of the genetics of the condition. Deletion of chromosome 15 is listed as the most common cause of PWS, accounting for roughly 70% of cases.

Maternal Uniparental Disomy (UPD), in which an individual has two copies of the maternal chromosome 15 (and no paternal 15), is said to account for about 25-30% of cases, with imprinting mutations or translocations accounting for the remaining few percent of cases.

However, parents of kids with PWS, especially those with younger children, look around and wonder about those statistics - there sure seem to be a lot of kids with PWS by UPD. Now a study out in the European Journal of Human Genetics confirms what some parents have suspected - there are a lot of kids with PWS by UPD. In fact, this study of PWS in the UK shows that 50% of kids with PWS under the age of 5 have PWS due to UPD.

 Why the apparent increase in PWS by UPD? For one thing, awareness is up and diagnostic testing has gotten better over the past 10 years or so - methylation analysis picks up both del and UPD with a high degree of accuracy, so more children with UPD may be diagnosed now compared to years past. Probably more important, this may represent an actual shift in the PWS population. Mothers now tend to be older when they have children. While the frequency of chromosome 15 deletion doesn't change with age, the frequency of 'nondisjunction', which leads to UPD, increases with age. It seems likely, then, that we'll need to get used to these new statistics.

 

JE Whittington et al. Changing rates of genetic subtypes of Prader-Willi syndrome in the UK . Eur J Hum Genet, 2006.


Topics: Research

Theresa Strong

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Theresa V. Strong, Ph.D., received a B.S. from Rutgers University and a Ph.D. in Medical Genetics from the University of Alabama at Birmingham (UAB). After postdoctoral studies with Dr. Francis Collins at the University of Michigan, she joined the UAB faculty, leading a research lab focused on gene therapy for cancer and directing UAB’s Vector Production Facility. Theresa is one of the founding members of FPWR and has directed FPWR’s grant program since its inception. In 2016, she transitioned to a full-time position as Director of Research Programs at FPWR. She remains an Adjunct Professor in the Department of Genetics at UAB. She and her husband Jim have four children, including a son with PWS.

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