Angelman syndrome - insights into a rare neurogenetic disorder.
Angelman syndrome is a rare neurogenetic disorder that is characterized by microcephaly, severe intellectual deficit, speech impairment, epilepsy, EEG abnormalities, ataxic movements, tongue protrusion, paroxysms of laughter, abnormal sleep patterns, and hyperactivity. Angelman syndrome results from loss of function of the imprinted UBE3A (ubiquitin-protein ligase E3A) gene on chromosome 15q11.2-q13. This loss of function can be caused by a mutation on the maternal allele, a 5-7 Mb deletion of the maternally inherited chromosomal region, paternal uniparental disomy of chromosome 15, or an imprinting defect. The chromosomal deletion tends to cause the most severe symptoms, possibly owing to co-deletion of GABA receptor genes. UBE3A mutations and imprinting defects can be associated with a high risk of recurrence within families. Disruption of UBE3A function in neurons seems to inhibit synapse formation and experience-dependent synapse remodelling. Clinical diagnosis of Angelman syndrome in infants and young children is sometimes difficult, but can be verified by genetic tests. At present, treatment of symptoms such as seizures is the only medical strategy, but genetic therapies aimed at activating the silent copy of UBE3A on the paternal allele are conceivable.
Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
Karin
K
Buiting
Raymond C. Philips Unit, Division of Genetics and Metabolism, Department of Pediatrics, University of Florida, 1600 SW Archer Road, PO Box 100296, Gainesville, Florida 32610-0296, USA.
Charles
C
Williams
Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
Bernhard
B
Horsthemke
D017204:Angelman Syndrome / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy*; D000818:Animals; D006801:Humans; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency* / Q000235:genetics
C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases