Inherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15

@article{Buiting1995InheritedMI,
  title={Inherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15},
  author={Karin Buiting and Shinji Saitoh and Stephanie Gross and B{\"a}rbel Dittrich and S Schwartz and Robert D. Nicholls and Bernhard Horsthemke},
  journal={Nature Genetics},
  year={1995},
  volume={9},
  pages={395-400}
}
A subset of patients with Angelman and Prader–Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DMA methylation at several loci within chromosome 15q11–13, and probably have a defect in imprinting. Using probes from a newly established 160–kb contig including D15S63 (PW71) and SNRPN, we have identified inherited microdeletions in two AS families and three PWS families. The deletions probably affect a single genetic element that we term the 15q11–13 imprinting… Expand
Imprinting in Prader–Willi and Angelman syndromes
TLDR
The identification of small deletions in a subgroup of patients in whom the loss of gene function is due to an incorrect imprint on the paternal or the maternal chromosome 15, respectively, has lead to the definition of a bipartite imprinting center that regulates in cis imprint resetting and imprint maintenance in the whole domain. Expand
Imprinting-mutation mechanisms in Prader-Willi syndrome.
TLDR
It is suggested that promoter elements at SNRPN play a key role in the initiation of imprint switching during spermatogenesis, since the epigenetic effect of an IM in the parental germ line determines the phenotypic effect in the patient. Expand
Imprinting in Prader-Willi and Angelman syndromes.
Imprinted genes are marked in the germline and retain molecular memory of their parental origin, resulting in allelic expression differences during development. Abnormalities in imprinted inheritanceExpand
Structure and function of the human chromosome 15 imprinting center
TLDR
The Prader‐Willi syndrome and the Angelman syndrome are distinct neurogenetic disorders that are caused by a deficiency of paternal or maternal contributions to chromosome 15, which appears to be instrumental in the regulation of gene activity. Expand
Molecular mechanism of angelman syndrome in two large families involves an imprinting mutation.
TLDR
Two large families are identified (AS-O and AS-F) segregating an AS imprinting mutation, including one family originally described in the first genetic linkage of AS to 15q11-q13, demonstrating that this original linkage is for the 15q 11-q 13 IC. Expand
Imprinting centre deletions in two PWS families: implications for diagnostic testing and genetic counselling
TLDR
Clinical and molecular findings in two families with a microdeletion affecting the chromosome 15 imprinting centre (IC) of Prader–Willi syndrome are reported, finding the silent transmission of PWS IC deletions through the female germline and the occurrence of neutral microdeletes close to the IC can impose considerable problems on diagnostic testing and genetic counselling in affected families. Expand
Imprinting in Angelman and Prader-Willi syndromes.
TLDR
Point mutations were found in the gene for E6-AP ubiquitin-protein ligase identifying it as the AS gene, and tissue-specific imprinting was shown in the human brain and in hippocampal neurons and Purkinje cells in the mouse. Expand
Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis.
TLDR
The molecular analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but no IC deletion concludes that the incorrect imprint in non-IC-deletion cases is the result of a spontaneous prezygotic or postzyGotic error, and that the paternal imprint may be the default imprint. Expand
Imprinting defects on human chromosome 15
TLDR
In the majority of patients with an imprinting defect, the incorrect imprint has arisen without a DNA sequence change, possibly as the result of stochastic errors of the imprinting process or the effect of exogenous factors. Expand
Prader–Willi syndrome and Angelman syndrome
  • K. Buiting
  • Biology, Medicine
  • American journal of medical genetics. Part C, Seminars in medical genetics
  • 2010
TLDR
Microdeletions in a small number of patients with PWS and AS have led to the identification of the chromosome 15 imprinting center (IC), which consists of two critical elements, which act in cis to regulate imprinting in the whole chromosome 15q11q13 imprinted domain. Expand
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TLDR
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