Newborn Screening for Prader-Willi and Angelman Syndromes

Funding Summary

Universal newborn screening for PWS will ensure that all babies with PWS are diagnosed at birth. Dr. Godler has developed a sensitive, accurate and cost-effective DNA test for detection of PWS and Angelman syndrome using the bloodspots (“heelprick”) obtained in all newborns.  In the study, FPWR is collaborating with with the Angelman Syndrome Foundation and the Victorian Medical Research Acceleration Fund to co-fund a pilot study in which Dr. Godler's group will screen 75,000 newborn blood spots to validate the assay so that it might be incorporated into newborn screening – providing early diagnosis and optimal care for babies with PWS, Angelman syndrome and another chromosome 15 alteration, dup15.  A newborn screening test will provide true incidence figures for PWS. 

Learn more in this short video!

 

Theresa Strong, Director of Research Programs, shares details on this project in this short video clip. 

Watch the full webinar describing the 11 research projects funded in this grant cycle here.

This grant was funded in part by a gift from the Storr Family Foundation. 

Lay Abstract

Prader-Willi (PWS) and Angelman (AS) syndromes are different genetic disorders caused by opposite effects of DNA methylation at the same genomic location. Both have a reported frequency of approximately 1 in 15,000 births and manifest intellectual disability. PWS is the most common genetic cause of life-threatening obesity; importantly, it can be effectively treated with hormone therapy and restricted diet if detected early. There is a strong case for including PWS and AS into newborn screening programs as there are clear benefits for affected infants and their families through early diagnosis and intervention. 

A key requirement for any new condition to be included in newborn screening is a test with high sensitivity and low cost ($1 to $3 per individual). The test must be ethical and ideally based on one or two 3 mm punches of dried blood spot material. Although DNA methylation testing of the SNRPN gene regulatory region detects most PWS (99%) and AS (78%) cases, use of one 3 mm punch of newborn blood spot material has not been validated in large population based studies. Dr Godler’s group has developed a novel, low-cost methylation test named Methylation Specific Quantitative Melt Analysis (MS-QMA) and shown that methylation testing of FMR1 can be used to effectively diagnose Fragile X syndrome (FXS), another relatively common genetic disorder (1 in 4000 in the general population). In 2015 the group was awarded an $800,000 grant from the National Health and Medical Research Council (NHMRC), Australia to perform a prevalence study for fragile X syndrome (FXS) on 100,000 newborns. Furthermore, in 2016, Foundation for Prader Willi Research (FPWR) awarded a 1 year grant to modify the first line MS-QMA screening and confirmatory testing protocol to include PWS and AS and to test performance of the developed pipeline on approximately 1000 newborn blood spots. This is a competitive renewal of the 2016 FPWR project to apply the automated screening cost-effective protocol developed in year 1, to 75,000 newborn blood spots remaining after completion of FXS testing for the NMHRC project.

This proposal will for the first time answer two important questions:

1) What is the current prevalence of PWS and AS in the general population?

2)  Is MS-QMA a feasible approach for combined newborn screening for FXS, PWS and AS? 

If successful, the next step would be inclusion of the SNRPN methylation assay into large scale FXS prospective newborn screening pilot studies in Australia and the USA through existing collaborations, coupled with health-economic assessments regarding expanding existing newborn screening programs globally to PWS, AS and FXS. This will ultimately improve outcomes for the affected children and their families through earlier diagnosis and intervention.

Research Outcomes:

Exploring autism symptoms in an Australian cohort of patients with Prader-Willi and Angelman syndromes. Baker EK, Godler D, Bui M, Hickerton C, Rogers C, Field M, Amor D, and Bretheton B. Journal of Neurodevelopmental Disorders. 2018,10:24 

Funded Year:

2018

Awarded to:

David Godler, PhD.

Amount:

$84,505

Institution:

Murdoch Children’s Research Institute

Researcher:

David Godler, PhD.

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