Update on the Cardiff Rett Syndrome Project

Article by Dr Angus Clarke, Cardiff University, written for Rett  News Autumn 2004.

"We are just about half way through the research project funded by The Health Foundation that is titled Clinical, molecular and social aspects of genetic testing for Rett syndrome. So far, Dr Hayley Archer has put a lot of time and effort into contacting families with information about the project and then gathering information and blood samples, where families are willing to participate in the research. This is helping us to develop our understanding of the connection between the clinical problems faced by affected girls and women – and sometimes by affected boys – and the underlying genetic mutations.

One particular interest has been refinement of the MECP2 mutation test so that it can detect large deletions within the gene. These can be harder to recognise in a female than the more usual and much smaller point mutations – because a structurally intact copy of the same gene will be present on the other X chromosome. This study has been a collaborative project with Dr Franco Laccone from Germany, and Hayley and he are reporting a series of patients with deletions of this type. At the same time – to allow this research to go ahead at all - Hayley and I have had to negotiate a dense forest of bureaucracy. There has not just been the usual and very proper requirement to obtain research ethics committee approval, which we expect and fully accept, but in addition a set of new requirements from almost every NHS Trust in the UK to fill out their individual Research & Development Office forms and even to keep them updated on our progress. This has been a frustrating waste of limited time.

While this has been going on, Dr Julie Evans has been working on mutations that might be harder to detect than the usual MECP2 mutations. She has found several changes in the gene STK9 in girls with a Rett-like pattern of disease but an early onset of seizures – typically within the first few months of life. This has been a collaborative effort with Dr John Christodoulou and his colleagues. We hope this joint work will continue with John and some of the other Australian researchers too. Because of these preliminary findings, we are keen to include in our project those girls or boys with an early onset of seizures and some, but not necessarily all, of the features of Rett syndrome, because a fair proportion of them may have STK9 mutations. If your daughter’s (or son’s) seizures started in their first year of life, we would be interested to hear from you. We cannot promise any genetic testing at this stage, but we would like to make contact - to let you know more about the study and to ask if you would be willing to fill out a questionnaire. If you are interested, do contact Dr Hayley Archer, Institute of Medical Genetics, University Hospital of Wales, Heath Park, Cardiff CF14 4XN.

We have also been looking elsewhere in the MECP2 gene for ‘hard-to-detect’ mutations, but so far without any definite success, and we are looking for other genes that could be relevant, perhaps linking in a functional way with the MECP2 or STK9 gene products.

The third component of the study started later than the others but is now getting on well – this is the set of interviews with YOU – with families – carried out by Dr Katie Featherstone, a social scientist. She is keen to find out about the experiences of families going through genetic testing for Rett syndrome – about the feelings it can generate, sometimes the good feelings but also the misunderstandings or confusions or upsets that can occur. I should add that Katie has also been studying us – the clinical and laboratory teams – so we know what it feels like. Once the tape recorder is running, however, it really is not a problem – and Katie can always turn it off if someone wants to say something really personal. We hope that this arm of the project will help doctors appreciate what is going on for families when they arrange genetic tests. We also hope that it may lead to publication of a book about Rett syndrome that puts over the views of families as well as of professionals.