If you are the parent of a child with Prader-Willi, Angelman or Chromosome 15 duplication (Dup15q) syndromes, or yourself have been tested and have been diagnosed with one of these disorders, the Free FX research team would like to invite you and your family members to participate in their study.

What is the research project about?

Prader-Willi, Angelman and Dup15q syndromes are distinct neurodevelopmental disorders caused by alterations in genes located in a specific region of the long arm of chromosome 15 (called 15q). This region contains genes, like SNRPN and UBE3A and others, which are very important for brain development. Unlike most other genes in the body, these genes behave differently depending on whether they are inherited from the mother (maternal) or from the father (paternal); this is a biological mechanism called 'genomic imprinting'.

Sometimes a child is born with differences in her/his chromosome 15 and/or in the genes located in the 15q region.

When there is paternal information missing from chromosome 15q, this causes Prader-Willi syndrome
When there is maternal information missing from chromosome 15q, this causes Angelman syndrome
When there is extra maternal information present from chromosome 15q, this causes Dup15q syndrome.

Overall, missing or extra genetic material at chromosome 15q is associated with the medical problems, intellectual disability, behavioural difficulties and autism, and these features are seen in individuals with Prader-Willi, Angelman and Dup15q syndromes which can all be considered imprinting disorders. In this study we will test a number of new highly accurate laboratory methods, which can tell us about a person's level of activity of the gene SNRPN, which is one of the genes on chromosome 15q. We want to find out how early after birth these tests can be used to predict intellectual disabilities, behavioural problems and autism in children and adults who have alterations of the SNRPN gene. We hope that this research will lead to earlier diagnosis and a better understanding of the needs of families with chromosome 15 disorders. This may lead to improvements in quality of life through earlier access to intervention programs aimed to unlock children's full potential in life.

What does taking part in the research project involve?

To take part in this study in Victoria, participants need to be under the age of 45. To take part in this study in New South Wales and Tasmania, participants need to be under the age of 20. Taking part in Victoria involves one visit at the Murdoch Children Research Institute (MCRI, based at the Royal Children's Hospital). Taking part in New South Wales involves one Visit at Hunter Genetics. Taking part in Tasmania involves one study visit at the clinics attached to the Royal Hobart Hospital.

During this visit we will take blood or saliva sample for some genetic testing and conduct an assessment of your and/or your child's behaviour, thinking and memory skills, which will involve for example being asked to solve puzzles and remember lists of words. The assessment will take approximately 3 hours. We will reimburse you a reasonable amount for your visit travel costs to the site of the appointment in order to participate in this project. Alternatively, we can organise a research assistant to come to your home to do the assessment. For the participants assessed in New South Wales and Tasmania, or for participants assessed at home, the study genetic counsellor may organise a separate time most convenient to the participants for blood or saliva samples to be collected.

What are the possible benefits of this research?

This research will help us to have a better understanding of the problems that are caused by specific alterations to the long arm of chromosome 15, and may help to develop better treatments and early intervention programs in the future. Depending on the outcomes of the assessments the team does for you and/or your child, they may be able to discuss any potential referral for specific intervention programs in the future. If you chose, the team can also provide you with the results of your genetic and psychological testing.

More information

If you would like more information about the project or to speak to a member of the research team, please contact:

Victoria and Tasmania: Ms Chriselle Hickerton, Research Genetic Counsellor, ph: 03 9936 6729 or 03 8341 6209, email: chriselle.hickerton@mcri.edu.au
New South Wales: Carolyn Rogers, Research Genetic Counsellor, ph: 02 4985 3100, email: carolyn.rorgers@hnehealth.nsw.gov.au

What is your expertise and experience?

I have a strong interest in gene therapy and its promise to treat or even cure many forms of human disease. I began my research career as a PhD student at the Murdoch Children's Research Institute by investigating different ways to effectively and safely introduce DNA into various human cell types. Following the completion of my PhD, I moved to Wisconsin (USA) for a postdoctoral position with Dr James Thomson acquiring experience with stem cell culture, reprogramming and gene editing. In 2011, I was lead author on a publication that was the first to report gene repair in patient-specific induced pluripotent stem cells. I recently returned to the Murdoch Children's Research Institute for a research fellowship and to continue to develop and apply my expertise in reprogramming and gene editing.

Where do you see opportunity for breakthroughs in Prader-Willi Syndrome?

Pluripotent stem cells can become any of the 220 cell types found in the human body so they offer enormous potential for studying human disease and drug discovery. iPS cells are particularly useful for studying Prader-Willi Syndrome because they can be used to derive the cells that are most affected but not easily accessible (e.g. those in the brain). I believe that one of the most exciting avenues of research is using genetically modified iPS cells in sophisticated "drug screening" assays to identify specific compounds that could be used to treat Prader-Willi Syndrome. People who have Prader-Willi retain at least one copy of the DNA region which is known to be involved in the syndrome, but this "maternal" copy is normally inactivated by epigenetic factors in a process known as genomic imprinting. My research explores the possibility of reactivating this maternal DNA region using therapeutic compounds.

Why are you involved in the Prader-Willi Research Foundation of Australia?

I have always loved being a scientist because of the thrill of discovery and sharing my knowledge with others. I'm excited that the Prader-Willi Research Foundation of Australia brings together passionate and dedicated people who bring a vast wealth of knowledge, resources and expertise to the table. What's more, we all share the same fundamental goal, to better the lives of people living with Prader-Willi Syndrome. I'm excited to think that my research could benefit the lives of children living with this syndrome.

Prader-Willi syndrome research: The Free FX study

Ask the Scientist: Dr Sara Howden