From electrophysiology to chromatin: a bottom-up approach to Angelman syndrome.
Angelman syndrome is one of the most studied human diseases related to a gene that is expressed on the maternal chromosome only in at least some brain cells. It is caused by inactivation of the UBE3A gene in the brain due to various abnormalities of the 15q11-q13 chromosome inherited from the mother. It is characterized by severe developmental delay, seizures, virtual absence of speech, motor impairment, and a particular behavioral phenotype. Studies of cortical, electromyographic and cerebellar electrophysiology in patients with Angelman syndrome and a mouse model revealed unique rhythmic neurophysiological activities in the cerebral cortex, cerebellar cortex, and muscles. The oscillatory patterns may be linked to molecular pathophysiology of the syndrome involving dysregulation of synaptic neurotransmission through UBE3A-related modulation of functional GABAA receptor complexes.
Dan
Bernard
B
Department of Neurology, University Children's Hospital Queen Fabiola, Free University of Brussels, 15 Avenue J.J. Crocq, 1020 Brussels, Belgium. bernard.dan@ulb.ac.be
Servais
Laurent
L
Boyd
Stewart G
SG
Wagstaff
Joseph
J
Cheron
Guy
G
D017204:Angelman Syndrome / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D002843:Chromatin / Q000502:physiology*; D002884:Chromosomes, Human, Pair 15; D004569:Electroencephalography; D004576:Electromyography; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
D002843:Chromatin; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases