Authors of a research letter in this week’s issue of THE LANCET-which investigated the occurrence of severe psychotic illness in adults with Prader Willi syndrome-suggest that susceptibility to psychotic illness in the general population could be influenced by genetic abnormalities on chromosome 15.
Prader Willi syndrome (PWS) is a genetically determined developmental disorder with an estimated birth incidence of 1 in 29,000 and population prevalence of around 1 in 52,000. The main features of the syndrome are reduced muscle tone at birth, impaired sexual development, extreme overeating, short stature, and mild learning disabilities. The two main genetic causes are deletions of genes of paternal origin from a specific part of chromosome 15, or the presence of two copies of chromosome 15 of maternal origin (maternal disomy). However, which exact gene (or genes), if absent, leads to PWS is unknown.
In a population-based study of PWS, Anthony Holland and colleagues from the University of Cambridge, and clinical services in Birmingham, UK, investigated the relation between genetic subtypes of PWS and psychiatric symptoms. Of 25 people with PWS aged 18 years or older, seven (28%) had severe affective disorder with psychotic features. The seven people with severe psychiatric disorder (all of whom were aged 28 years or older) included all five patients with the rarer disomy 15 form of PWS, one person had the more common deletion form, and one other had a very rare genetic variant of PWS (an imprinting centre mutation). The investigators postulate that in people with PWS due to chromosome 15 disomy, an abnormal pattern of expression of a sex-specific imprinted gene on that chromosome is associated with psychotic illness in early adult life.
Anthony Holland comments: “If this hypothesis is correct, allelic variation of this imprinted gene could be one cause of genetic vulnerability to psychotic illness in the general population.”
Contact: Dr Anthony Holland, Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, 18b Trumpington Road, Cambridge CB2 2AH, UK; T) +44 (0)1223 746112; F) +44 (0)1223 746122; E) ajh1008@cam.ac.uk
Journal
The Lancet