Prader-Willi Syndrome Research Today is a free monthly online journal that collates and summarizes the latest research about Prader-Willi Syndrome, including details on pws, symptoms, treatment, causes.

Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader-Willi syndrome.

Relkovic D, Doe CM, Humby T, Johnstone KA, Resnick JL, Holland AJ, Hagan JJ, Wilkinson LS, Isles AR

Laboratory of Cognitive and Behavioural Neuroscience, The Babraham Institute, Babraham Research Campus, Cambridge, UK.

Abstract The genes in the imprinted cluster on human chromosome 15q11-q13 are known to contribute to psychiatric conditions such as schizophrenia and autism. Major disruptions of this interval leading to a lack of paternal allele expression give rise to Prader-Willi syndrome (PWS), a neurodevelopmental disorder with core symptoms of a failure to thrive in infancy and, on emergence from infancy, learning disabilities and over-eating. Individuals with PWS also display a number of behavioural problems and an increased incidence of neuropsychiatric abnormalities, which recent work indicates involve aspects of frontal dysfunction. To begin to examine the contribution of genes in this interval to relevant psychological and behavioural phenotypes, we exploited the imprinting centre (IC) deletion mouse model for PWS (PWS-IC(+/-)) and the five-choice serial reaction time task (5-CSRTT), which is primarily an assay of visuospatial attention and response control that is highly sensitive to frontal manipulations. Locomotor activity, open-field behaviour and sensorimotor gating were also assessed. PWS-IC(+/-) mice displayed reduced locomotor activity, increased acoustic startle responses and decreased prepulse inhibition of startle responses. In the 5-CSRTT, the PWS-IC(+/-) mice showed deficits in discriminative response accuracy, increased correct reaction times and increased omissions. Task manipulations confirmed that these differences were likely to be due to impaired attention. Our data recapitulate several aspects of the PWS clinical condition, including findings consistent with frontal abnormalities, and may indicate novel contributions of the imprinted genes found in 15q11-q13 to behavioural and cognitive function generally.

Published 22 January 2010 in Eur J Neurosci, 31(1): 156-64.
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Articles on Prader-Willi Syndrome published 21 January 2010:

The C15orf2 gene in the Prader-Willi syndrome region is subject to genomic imprinting and positive selection.   Neurogenetics.

C15orf2 (Chromosome 15 open reading frame 2) is an intronless gene, which is located in the Prader-Willi syndrome (PWS) chromosomal region on human chromosome 15. Mice do not have an orthologous gene. Here we show that expression of C15orf2 in the fetal human brain is imprinted. Using Western blot and immunohistological studies we have obtained evidence that C15orf2 protein is present in several regions of the brain. Previously published phylogenetic studies as well as population genetic ... [Abstract] [Full-text]

Metabolic syndrome in children with Prader-Willi syndrome: the effect of obesity.   Nutr Metab Cardiovasc Dis.

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS), the most frequent syndromic obesity, is associated with elevated morbidity and mortality in pediatric and adult ages. In PWS, the presence of metabolic syndrome (MS) has not yet been established. The aim of the study was to estimate the frequency of MS and its components in pediatric subjects according to obesity status. METHODS AND RESULTS: A cross-sectional study was performed in 109 PWS children aged 2-18years (50 obese and 59 non-obese) and ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 19 January 2010:

Deletions and duplications of the 15q11-q13 region in spermatozoa from Prader-Willi syndrome fathers.   Mol Hum Reprod.

Prader-Willi syndrome (PWS) is a genomic disorder mostly caused by deletions of 15q11-q13 region (70%). It has been suggested that the particular genomic architecture of 15q11-q13 region, characterized to be flanked by Low Copy Repeats (LCR), could predispose it to Non Allelic Homologous Recombination (NAHR). However, no studies in gametes of fathers of PWS individuals have been published to date. The objective of the study was to assess the incidence of 15q11-q13 deletions and duplications in ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 18 January 2010:

An interstitial 15q11-q14 deletion: Expanded Prader-Willi syndrome phenotype.   Am J Med Genet A.

We present an infant girl with a de novo interstitial deletion of the chromosome 15q11-q14 region, larger than the typical deletion seen in Prader-Willi syndrome (PWS). She presented with features seen in PWS including hypotonia, a poor suck, feeding problems, and mild micrognathia. She also presented with features not typically seen in PWS such as preauricular ear tags, a high-arched palate, edematous feet, coarctation of the aorta, a PDA, and a bicuspid aortic valve. G-banded chromosome ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 11 January 2010:

Systemic disorders and their influence on the development of dental hard tissues: A literature review.   J Dent.

OBJECTIVES: This report highlights the influence of a number of disorders with systemic physiological effects that impact on the development of dental hard tissues. It focuses in particular, on the pathological effects of systemic conditions with less well recognised, but no less important, impacts on dental development. Such conditions, include cystic fibrosis, HIV/AIDS, leukaemia, Alstrom syndrome, hypophosphatasia, Prader-Willi syndrome, Tricho-dento-osseous syndrome, tuberous sclerosis, ... [Abstract] [Full-text]

Long-Term Growth Hormone Therapy Changes the Natural History of Body Composition and Motor Function in Children with Prader-Willi Syndrome.   J Clin Endocrinol Metab.

Background: Children with Prader-Willi syndrome (PWS) have decreased muscle mass, hypotonia, and impaired linear growth. Recombinant human GH (hGH) treatment reportedly improves body composition and physical function in children with PWS, but these studies lack long-term control data. To assess the impact of hGH therapy begun early in life on the natural history of PWS, we compared height, body composition, and strength in similar-age children with PWS naïve to hGH with those treated with hGH ... [Abstract] [Full-text]

Correlation of Adiponectin Receptor Expression with Cytokines and Insulin Sensitivity in Growth Hormone (GH)-Treated Children with Prader-Willi Syndrome and in Non-GH-Treated Obese Children.   J Clin Endocrinol Metab.

Context: Prader-Willi syndrome (PWS), a genetic disorder characterized by obesity in early childhood, is reported to have elevated levels of adiponectin. The effects of adiponectin are mediated by adiponectin receptors (ADIPORs) that include ADIPOR1 and ADIPOR2. There is evidence that several cytokines including adiponectin, TNF-alpha, and IL-6, are involved in insulin sensitivity. Objective and Methods: We measured the relative expression of adiponectin, ADIPORs, several proinflammatory ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 8 January 2010:

Long-term safety of recombinant human growth hormone in children.   J Clin Endocrinol Metab, 95(1): 167-77.

BACKGROUND: Between 1985 and 2006, the National Cooperative Growth Study (NCGS) monitored the safety and efficacy of recombinant human growth hormone (rhGH) in 54,996 children. METHODS: Enrolled patients were followed until rhGH discontinuation. Investigators submitted adverse event reports for targeted events or those potentially rhGH-related. RESULTS: Early concerns about de novo leukemia in patients without risk factors have not been substantiated--three observed vs. 5.6 expected in ... [Abstract] [Full-text]

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