Article

Prader-Willi and Angelman syndromes: sister imprinted disorders.

University of California, Irvine, USA.
American Journal of Medical Genetics (Impact Factor: 3.23). 02/2000; 97(2):136-46.
Source: PubMed

ABSTRACT Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct complex disorders mapped to chromosome 15q11-q13. They both have characteristic neurologic, developmental, and behavioral phenotypes plus other structural and functional abnormalities. However, the cognitive and neurologic impairment is more severe in AS, including seizures and ataxia. The behavioral and endocrine disorders are more severe in PWS, including obsessive-compulsive symptoms and hypothalamic insufficiency. Both disorders can result from microdeletion, uniparental disomy, or an imprinting center defect in 15q11-q13, although the abnormality is on the paternally derived chromosome 15 for PWS and the maternally derived 15 for AS because of genomic imprinting. Although the same gene may control imprinting for both disorders, the gene(s) causing their phenotypes differ. AS results from underexpression of a single gene, UBE3A, which codes for E6-AP, a protein that functions to transfer small ubiquitin molecules to certain target proteins, to enable their degradation. The genes responsible for PWS are not determined, although several maternally imprinted genes in 15q11-q13 are known. The most likely candidate is SNRPN, which codes for a small nuclear ribonucleoprotein, a ribosome-associated protein that controls gene splicing and thus synthesis of critical proteins in the brain. Animal models exist for both disorders. The genetic relationship between PWS and AS makes them unique and potentially highly instructive disorders that contribute substantially to the population burden of cognitive impairment.

0 Bookmarks
 · 
114 Views
  • Source
    Archivos argentinos de pediatría 10/2013; 111(5):e117-e120. DOI:10.5546/aap.2013.e117 · 0.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The ability to examine epigenetic mechanisms in the brain has become readily available over the last 20 years. This has led to an explosion of research and interest in neural and behavioral epigenetics. Of particular interest to researchers, and indeed the lay public, is the possibility that epigenetic processes, such as changes in DNA-methylation and histone modification, may provide a biochemical record of environmental effects. This has led to some fascinating insights into how molecular changes in the brain can control behavior. However, some of this research has also attracted controversy and, as is dealt with here, some overblown claims. This latter problem is partly linked to the shifting sands of what is defined as “epigenetics”. In this review I provide an overview of what exactly epigenetics is, and what is hype, with the aim of opening up a debate as to how this exciting field moves forward.
    Genes Brain and Behavior 10/2014; DOI:10.1111/gbb.12184 · 3.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features consist of neonatal hypotonia, distinctive facial features, delayed overall development with mental deficiency, behavioral abnormalities, poor growth in infancy followed by overeating with severe obesity, short stature, and hypogonadism. Recently, patients with PWS have been diagnosed at an earlier age, especially in the neonatal period. In addition, early interventions such as commencement of growth hormone therapy and dietary programs, have received attention in PWS treatment. Since early diagnosis is now possible based on both clinical symptoms and signs and on molecular genetic criteria, early dietary intervention and early growth hormone therapy during the first two years may improve neurodevelopment, increase muscle mass, and reduce obesity. Our aim in this review is to document the characteristics of infants with PWS and to provide a recent update regarding early management.
    01/2012; 17(3):145. DOI:10.6065/apem.2012.17.3.145