Molecular and Clinical Aspects of Angelman Syndrome

Molecular Syndromology

A. Dagli¹  K. Buiting¹  C.A. Williams¹ 

[1] aRaymond C. Philips Unit, Division of Genetics and Metabolism, Department of Pediatrics, University of Florida, Gainesville, Fla., USA

关键词: Angelman syndrome;    Imprinting;    Microdeletion;    15q11.2–q13;    UBE3A;    Ubiquitin;   

DOI  :  10.1159/000328837

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2–q13 genomic region identifies 75–80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5–10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity.

【 授权许可】

Unknown