Different distribution of the genetic subtypes of the Prader–Willi syndrome in the elderly
- 12 May 2010
- journal article
- Published by Springer Science and Business Media LLC in European Journal of Human Genetics
- Vol. 18 (9), 993-998
- https://doi.org/10.1038/ejhg.2010.67
Abstract
The Prader–Willi syndrome (PWS) is a genetic disorder caused by the absent expression of the paternal copy of maternally imprinted genes in chromosome region 15q11–13. The frequencies of different subtypes in PWS are usually given in literature as 70% deletion, 25–30% maternal uniparental disomy (mUPD) and 3–5% others (imprinting centre (IC) defects and translocations). Little is known about factors that influence the frequency of genetic subtypes in PWS. The study sample comprised 102 adults with clinically and genetically confirmed PWS, contacted through the Dutch Prader–Willi Parent Association and through physicians specialized in treating persons with intellectual disabilities. Genetic testing showed 55 persons (54%) with a paternal deletion, 44 persons (43%) with an mUPD and 3 persons (3%) with a defect of the IC. The observed distribution in our study differed from that in literature (70% deletion, 30% mUPD), which was statistically significant (z-score: P<0.05). This was mainly caused by a higher proportion of mUPD in the advanced age groups. Differences in maternal age and BMI of persons with PWS could not explain the differences in distribution across the age groups. Our study population had a much broader age range, compared with other studies, because of a predominance of elderly people (40+ years) with PWS. In other studies, these elderly persons might have been undiagnosed and/or underreported because of a lack of genetic diagnosis. The results underline both the need for correct genetic diagnosis in all persons with PWS and adjustment of the guidelines for preventive management in adulthood.This publication has 32 references indexed in Scilit:
- Imprinting disorders and assisted reproductive technologyFertility and Sterility, 2009
- Prader–Willi syndromeEuropean Journal of Human Genetics, 2008
- Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA clusterNature Genetics, 2008
- A systematic review of mortality in schizophrenia - Is the differential mortality gap worsening over time?Archives of General Psychiatry, 2007
- Neural Mechanisms Underlying Hyperphagia in Prader‐Willi SyndromeObesity, 2006
- Mortality in Prader-Willi SyndromeAmerican Journal on Mental Retardation, 2006
- Prader–Willi syndrome: Causes of death in an international series of 27 casesAmerican Journal of Medical Genetics Part A, 2003
- Inherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15Nature Genetics, 1995
- Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype?American Journal of Medical Genetics, 1994
- Deletions of Chromosome 15 as a Cause of the Prader–Willi SyndromeThe New England Journal of Medicine, 1981