The genetics of Rett
syndrome and genotype-phenotype relationships
One of the projects to be funded by the
Jeans-for-Genes money is a collaborative project, led by myself, to
investigate the genetics of Rett syndrome and genotype-phenotype
relationships in more detail than has hitherto been attempted. Together with
Dr Tony Charman, Institute of Child Health, London, Dr Alison Kerr and
others, we are currently studying more than 230 UK patients with classic or
atypical Rett syndrome. We are investigating whether the severity of the
disorder tends to be related to the kind of DNA alteration found in MECP2,
the gene that causes >80% of classic and many atypical cases, in patients,
and whether there are any subtle patterns in the severity of any groups of
clinical or behavioural signs.
Dr Charman and Dr Bailey are approaching the end
point of the current phase of this project (watch out for reports of their
findings in the scientific press in due course - they'll also write a lay
summary for a future edition of Rett News). Together with Prof Angus Clarke
and Dr Hayley Archer in Cardiff and Pro. Maj Hulten in Warwick, our
collaborative team will take this approach further, with the help of the J4G
money, to increase the sample size to more than 300 patients, and to
investigate additional aspects of the genetics of Rett syndrome. In
particular, we intend to find out the effect of differing extents of X
chromosome inactivation on the relationship between mutation and severity by
sampling multiple tissues, to make 'cell lines' that will act as a resource
for future studies on the biology of cells from Rett syndrome patients with
particular mutations, to investigate the effect of other variants in the
MECP2 gene on the action of known mutations, and to identify a set of
patients without identifiable MECP2 mutations in whom to search for other
mechanisms responsible for causing the disorder i.e. to look for mutations
in other genes.
To assist with the last of these, we also intend
to establish a Europe-wide resource of cells from families with more than
one affected case, many of whom do not have MECP2 mutations. Over the two
years of J4G funding, our team hopes to make a significant contribution to
the genetic and clinical understanding of Rett syndrome, and looks forward
to working closely with many of the UK families of Rett girls, women and
indeed boys.
Dr Mark E.S. Bailey, Lecturer
and Coordinator of Postgraduate Studies, Division of Molecular Genetics,
Institute of Biomedical and Life Sciences (IBLS), University of Glasgow,
Anderson College, 56 Dumbarton Rd, Glasgow G11 6NU
March 2004
