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.

Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells.

Asai T, Liu Y, Di Giandomenico S, Bae N, Ndiaye-Lobry D, Deblasio A, Menendez S, Antipin Y, Reva B, Wevrick R, Nimer SD

Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, United States;

We recently defined a critical role for p53 in regulating the quiescence of adult hematopoietic stem cells (HSCs), and identified necdin as a candidate p53 target gene. Necdin is a growth suppressing protein and the gene encoding necdin is one of several genes that are deleted in individuals with Prader-Willi syndrome. To define the intrinsic role of necdin in adult hematopoiesis, we transplanted necdin null fetal liver cells into lethally irradiated recipients. We show that necdin null adult HSCs are less quiescent and more proliferative than normal, demonstrating the similar role of necdin and p53 in promoting HSC quiescence during steady state. However, wild type recipients repopulated with necdin null hematopoietic stem/progenitor cells (HSPCs) show enhanced sensitivity to irradiation and chemotherapy, with increased p53-dependent apoptosis, and increased myelosuppression and mortality. Necdin controls the HSC response to genotoxic stress via both cell cycle-dependent and -independent mechanisms, with the latter occurring in a Gas2L3-dependent manner. Thus, we find that necdin functions as a molecular switch in adult hematopoiesis, acting in a p53-like manner to promote HSC quiescence in the steady state, but suppressing p53-dependent apoptosis in response to genotoxic stress.

Published 10 July 2012 in Blood.
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Articles on Prader-Willi Syndrome published 9 July 2012:

Beneficial effects of growth hormone treatment on cognition in children with prader-willi syndrome: a randomized controlled trial and longitudinal study.   J Clin Endocrinol Metab, 97(7): 2307-14.

Background: Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited. Methods: Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study during 4 yr of GH treatment. Cognitive functioning was measured biennially by short forms of the WPPSI-R or WISC-R, depending on age. Total IQ (TIQ) score was estimated based on two subtest scores. Results: ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 4 July 2012:

The imprinted NPAP1/C15orf2 gene in the Prader-Willi syndrome region encodes a nuclear pore complex associated protein.   Hum Mol Genet.

The Prader-Willi syndrome (PWS) region in 15q11q13 harbours a cluster of imprinted genes expressed from the paternal chromosome only. Whereas loss of function of the SNORD116 genes appears to be responsible for the major features of PWS, the role of the other genes is less clear. One of these genes is C15orf2, which has no orthologues in rodents, but appears to be under strong positive selection in primates. C15orf2 encodes a 1156 amino acid protein with six nuclear localisation sequences. By ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 29 June 2012:

Chromosomal microarray analysis of functional Xq27-qter disomy and deletion 3p26.3 in a boy with Prader-Willi like features and hypotonia.   Eur J Med Genet.

Duplications of the long arm of the X chromosome are rare. The infantile phenotype shares some resemblance with the Prader-Willi syndrome, presenting severe psychomotor retardation, facial dysmorphic features with a broad face, a small mouth and a thin pointed nose, hypotonia, urogenital malformation and proneness to infections. We report a boy with an additional Xq27-qter chromosome segment translocated onto the short arm of chromosome 3. The karyotype was 46,XY,der(3)t(X;3)(q27.3; p26.3)mat. ... [Abstract] [Full-text]

Hypothalamic expression of snoRNA Snord116 is consistent with a link to the hyperphagia and obesity symptoms of Prader-Willi syndrome.   Int J Dev Neurosci.

The hypothalamus is integral to the regulation of body homeostasis, including food intake, energy balance, and blood pressure. Dysfunction of the hypothalamus has been associated with a broad range of disorders; many of which are sex-dependent in prevalence. Small nucleolar (sno) RNAs are a group of small RNAs located in nucleoli that modulate chemical modifications and maturation of ribosomal or other RNAs. Recent data suggest that snoRNA Snord116 is important for the pathogenesis of ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 22 June 2012:

Ovarian Function and Reproductive Hormone Levels in Girls with Prader-Willi Syndrome: A Longitudinal Study.   J Clin Endocrinol Metab.

Context:The etiology of hypogonadism in girls with Prader-Willi syndrome (PWS) remains uncertain.Objectives:The aim of the study was to evaluate gonadal function longitudinally in girls and female adolescents with PWS.Measurements:We performed a longitudinal assessment of anti-Müllerian hormone (AMH), gonadotropins, estradiol (E(2)), inhibin B and A, and pubertal development in girls and female adolescents with PWS.Patients and Methods:Sixty-one girls participating in the Dutch PWS Cohort ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 21 June 2012:

De Novo Unbalanced Translocations in Prader-Willi and Angelman Syndrome Might Be the Reciprocal Product of inv dup(15)s.   PLoS One, 7(6): e39180.

The 15q11-q13 region is characterized by high instability, caused by the presence of several paralogous segmental duplications. Although most mechanisms dealing with cryptic deletions and amplifications have been at least partly characterized, little is known about the rare translocations involving this region. We characterized at the molecular level five unbalanced translocations, including a jumping one, having most of 15q transposed to the end of another chromosome, whereas the ... [Abstract] [Full-text]

Stress, locus of control, and family cohesion and adaptability in parents of children with down, williams, fragile x, and prader-willi syndromes.   Am J Intellect Dev Disabil, 117(3): 207-24.

Abstract The present study analyzes differences in parental stress in families of children with Down, Williams, Fragile X, and Prader-Willi syndromes, exploring factors that influence parental stress, such as child's characteristics, parental locus of control, and family cohesion and adaptability. Differences between mothers and fathers are also investigated. Parents were given self-report questionnaires to assess family stress, parental locus of control, and family cohesion and adaptability. ... [Abstract] [Full-text]

Articles on Prader-Willi Syndrome published 19 June 2012:

Scoliosis in Prader-Willi syndrome: Effect of growth hormone therapy and value of paravertebral muscle volume by CT in predicting scoliosis progression.   Am J Med Genet A, 158(7): 1628-32.

Growth hormone (GH) therapy is now widely given to Prader-Willi syndrome (PWS) patients to encourage growth in body height and to prevent obesity. Scoliosis, one of the complications in this syndrome, is thought to be accelerated in parallel with a rapid increase in body height, especially during adolescence. To determine whether GH therapy aggravates scoliosis and to identify any factor which might predict the progression of scoliosis, we studied 35 (22 males and 13 female) PWS patients ... [Abstract] [Full-text]

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