Genetic and clinical advances in Prader-Willi syndrome

Wharton, Robert H.; Loechner, Karen J.

doi:10.1097/00008480-199612000-00013

Cited by 30 publications

(15 citation statements)

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“…Abnormal ventilatory responses to hyperoxia, hypoxia, and hypercapnia when awake and sleeping are noted in PWS patients Gozal et al, 1994;Schluter et al, 1997;Menendez, 1999). Furthermore, there are reports of sleep-related central and obstructive apnea (Clift et al, 1994;Wharton and Loechner, 1996;Manni et al, 2001;Nixon and Brouillette, 2002). A report of a 29 week premature infant with PWS who required prolonged ventilatory support points to a prenatal onset of respiratory dysfunction in PWS (MacDonald and Camp, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…The major manifestations of PWS include neonatal hypotonia and failure to thrive, followed by childhood-onset developmental delay and obesity. Infants with PWS have significant respiratory abnormalities, including sleep-related central and obstructive apneas and reduced response to changes in oxygen and CO 2 levels Clift et al, 1994;Gozal et al, 1994;Wharton and Loechner, 1996;Schluter et al, 1997;Menendez, 1999;Manni et al, 2001;Nixon and Brouillette, 2002). A subset of genes in the region deleted in PWS, including the NDN gene encoding necdin, are active only on the paternally inherited allele and silenced by imprinting on the maternal allele (Nicholls, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Absence ofNdn, Encoding the Prader-Willi Syndrome-Deleted Genenecdin, Results in Congenital Deficiency of Central Respiratory Drive in Neonatal Mice

et al. 2003

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necdin (Ndn) is one of a cluster of genes deleted in the neurodevelopmental disorder Prader-Willi syndrome. necdin is upregulated during neuronal differentiation and is thought to play a role in cell cycle arrest in terminally differentiated neurons. Most necdin-deficient Ndn tm2Stw mutant pups carrying a targeted replacement of Ndn with a lacZ reporter gene die in the neonatal period of apparent respiratory insufficiency. We now demonstrate that the defect can be explained by abnormal neuronal activity within the putative respiratory rhythm-generating center, the pre-Bötzinger complex. Specifically, the rhythm is unstable with prolonged periods of depression of respiratory rhythmogenesis. These observations suggest that the developing respiratory center is particularly sensitive to loss of necdin activity and may reflect abnormalities of respiratory rhythm-generating neurons or conditioning neuromodulatory drive. We propose that necdin deficiency may contribute to observed respiratory abnormalities in individuals with Prader-Willi syndrome through a similar suppression of central respiratory drive.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Absence ofNdn, Encoding the Prader-Willi Syndrome-Deleted Genenecdin, Results in Congenital Deficiency of Central Respiratory Drive in Neonatal Mice

et al. 2003

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“…Approximately 70% of the cases have a de novo deletion in the paternally inherited chromosome 15q11-q13 region. The remaining cases occur as a result of a maternal uniparental disomy (UPD) of chromosome 15 (20-25%) or as a result of either microdeletions or epimutations in the 15q11-q13 region (2-5%) (17,19). No single gene mutation has been found that explains all the features of PWS.…”

Section: Prader-willi Syndromementioning

confidence: 99%

Syndromic Disorders with Short Stature

Şıklar¹,

Berberoğlu²

2014

Jcrpe

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Short stature is one of the major components of many dysmorphic syndromes. Growth failure may be due to a wide variety of mechanisms, either related to the growth hormone (GH)/insulin-like growth factor axis or to underlying unknown pathologies. In this review, the relatively more frequently seen syndromes with short stature (Noonan syndrome, Prader-Willi syndrome, Silver-Russell syndrome and Aarskog-Scott syndrome) were discussed. These disorders are associated with a number of endocrinopathies, as well as with developmental, systemic and behavioral issues. At present, GH therapy is used in most syndromic disorders, although long-term studies evaluating this treatment are insufficient and some controversies exist with regard to GH dose, optimal age to begin therapy and adverse effects. Before starting GH treatment, patients with syndromic disorders should be evaluated extensively.

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“…PWS results from the lack of paternal expression of the q11–q13 region of chromosome 15, caused by deletion, uniparental disomy, imprinting centre defect causing maternal imprinting or balanced translocation 5 – 12. Hypothalamic dysfunction may be responsible for many features of PWS 13 – 15.…”

mentioning

confidence: 99%