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Angelman syndrome

par Dan, Bernard ;Boyd, Stewart G.
Editeur scientifique Andermann, Frederick;Shorvon, S.;Guerrini, R
Référence The causes of epilepsy, common and uncommon causes in adults and children, Cambridge University Press, Cambridge, page (201-205)
Publication Publié, 2011

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Résumé :

Angelman syndrome is characterized by developmental delay, absence of speech, motor impairment, epilepsy, and a peculiar behavioral phenotype with happy demeanor (Dan2008). It is caused by lack of expression of the UBE3A gene, which can result from various abnormalities of chromosome 15q11–q13. Similar chromosome 15q11–q13 abnormalities result in either Angelman syndrome if they concern the chromosome inherited from the mother, or Prader–Willi syndrome (a clinically distinct condition with hypotonia, learning difficulties, obesity, and hypogonadism) if they concern the chromosome of paternal origin, illustrating the phenomenon of genomic imprinting. In about 70% of patients, Angelman syndrome is due to a de novo 15q11–q13 microdeletion on the maternally inherited chromosome that can be detected with fluorescence in situ hybridization (FISH). Approximately 2–3% of patients have inherited both copies of chromosome 15 from the father and none from the mother, i.e., paternal uniparental disomy. As a result, no functional copy of UBE3A is inherited from the mother. These patients statistically show a less severe phenotype than those with a deletion, with larger head circumference, less severe epilepsy, and more words, although eventual speech remains extremely limited (Lossie et al. 2001). Another 3–5% of patients have an imprinting defect resulting in the absence of the typical maternal pattern of DNA methylation. Phenotypically, they are indistinguishable from patients with uniparental disomy (Lossie et al. 2001). There is a mutation in the maternal UBE3A gene in 5–10% of patients, with high occurrence of private, de novo mutations.