MRI study of neural endophenotypes in Prader-Willi Syndrome.
Research type
Research Study
Full title
Investigating neural endophenotypes in Prader-Willi Syndrome (PWS): brain structure, function and connectivity in 15q11-13 deletion and maternal uniparental disomy 15 and potential implications in the cognitive and behavioural phenotypes.
IRAS ID
135847
Contact name
Katherine Manning
Contact email
Sponsor organisation
CPFT
Research summary
Prader-Willi syndrome (PWS) is a disorder of genomic imprinting, resulting in the lack of paternally expressed genes at chromosomal locus 15q11-13. Most prominently, PWS results in a severe overeating disorder and intellectual disability, but many individuals also experience a range of social, behavioural and psychiatric difficulties.
PWS arises most commonly from one of two genetic events: paternal deletion and maternal uniparental disomy (mUPD). Research has indicated that, as well as variation between individuals, certain features associated with PWS may vary in prevalence or severity according to genetic subtype. For example, greater autistic traits and psychiatric disturbance have been reported in the mUPD subtype, an differences in the cognitive profile have also been described.
While the genetic and behavioural/cognitive levels of PWS are relatively well-characterised, with the exception of the eating behaviour, much less is known about what is happening in the PWS brain and how this might relate to the phenotype. Furthermore, where the neural level has been considered, structure and function have typically been considered in isolation and potential differences between genetic subtypes rarely investigated. However, the sum of research to date alongside the range of features associated with PWS, indicates aberrant activity across widespread neural networks.
Consequently, this study aims to investigate neural structure and functional connectivity in PWS using magnetic resonance imaging, in comparison to a group of typically-developing individuals as well as between genetic subtypes. Further, this study also aims to consider potential relationships between any alterations in neural function and/or structure and behavioural, social and psychiatric features.
Additionally, in collaboration with Dr Livesey of the Gurdon Institute, skin biopsies from 6 participants will be used to create neuronal cells from pluripotent stem cells. This will enable the study of how differences between genetic subtypes at the level of the brain are mirrored at the cellular level in the laboratory.
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
13/EE/0373
Date of REC Opinion
8 Jan 2014
REC opinion
Further Information Favourable Opinion