Encyclopedia of Molecular Mechanisms of Disease

2009 Edition
| Editors: Florian Lang

Angelman Syndrome

  • Alessandra Baumer
Reference work entry
DOI: https://doi.org/10.1007/978-3-540-29676-8_107
How to cite

Synonyms

MIM 105830; Former designation (now in disuse): “Happy puppet syndrome”

Definition and Characteristics

Angelman syndrome (AS) is a neurogenetic disorder caused by genetic defects at 15q11–13. Characteristic features include severe mental retardation, lack of speech, unmotivated laughter, and ataxia.

Prevalence

The disorder occurs in approximately 1/15,000–20,000 live births.

Genes

E6-associated protein ubiquitin-protein ligase gene: UBE3A (MIM: 601623); Small nuclear ribonucleoprotein polypeptide N: SNRPN (MIM: 182279).

Molecular and Systemic Pathophysiology

The genetic basis of AS is complex. The majority of patients (approximately 70%) have an interstitial deletion at 15q11–q13 affecting the maternally inherited chromosome 15. Approximately 5% of AS patients have an imprinting defect [1] and 3–5% have a paternal UPD15 [2]. Furthermore, mutations in the imprinted gene UBE3A account for approximately 10% of AS cases [3, 4, 5]. The genetic defect underlying the remaining 10%...

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References

  1. 1.
    Buiting K, Dittrich B, Gross S, Lich C, Farber C, Buchholz T, Smith E, Reis A, Burger J, Nothen MM, Barth-Witte U, Janssen B et al. (1998) Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis. Am J Hum Genet 63:170–180PubMedGoogle Scholar
  2. 2.
    Malcolm S, Clayton-Smith J, Nichols M, Robb S, Webb T, Armour JAL, Jeffreys AJ, Pembrey ME (1991) Uniparental paternal disomy in Angelman's syndrome. Lancet 337:694–697PubMedGoogle Scholar
  3. 3.
    Kishino T, Lalande M, Wagstaff J (1997) UBE3A/E6-AP mutations cause Angelman syndrome. Nature Genet 15:70–73PubMedGoogle Scholar
  4. 4.
    Matsuura T, Sutcliffe JS, Fang P, Galjaard R-J, Jiang Y, Benton CS, Rommens JM, Beaudet AL (1997) De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nature Genet 15:74–77PubMedGoogle Scholar
  5. 5.
    Baumer A, Balmer D, Schinzel A (1999) Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria. Hum Genet 105:598–602PubMedGoogle Scholar
  6. 6.
    Lossie AC, Whitney MM, Amidon D, Dong HJ, Chen P, Theriaque D, Hutson A, Nicholls RD, Zori RT, Williams CA, Driscoll DJ (2001) Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J Med Genet 38:834–845PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Berlin Heidelberg 2009

Authors and Affiliations

  • Alessandra Baumer
    • 1
  1. 1.Institute of Medical GeneticsUniversity of ZurichZurichSwitzerland