Disease relevance of Angelman Syndrome

• In contrast to our findings for patients with Prader-Willi syndrome, in which maternal UPD was common, our data demonstrate that paternal UPD is infrequent in patients with Angelman syndrome [1].
• Phenotypic differences in Angelman syndrome patients: imprinting mutations show less frequently microcephaly and hypopigmentation than deletions [2].
• Levodopa responsive Parkinsonism in adults with Angelman Syndrome [3].
• We report a 26-month-old boy with Angelman syndrome associated with Lennox-Gastaut syndrome, who developed a rash and a persistent toxic hepatitis after lamotrigine was added to valproate therapy [4].
• The ocular findings of fundal/iris hypopigmentation and strabismus with minimal refractive error in conjunction with the cognitive, behavioral, and motoric characteristics the patient exhibits may be the first clues for the diagnosis of Angelman Syndrome in a developmentally delayed child [5].

Psychiatry related information on Angelman Syndrome

• Disruption of the maternal copy of E6-AP is correlated with Angelman syndrome (AS), a genetic neurological disorder characterized by severe mental retardation, seizures, speech impairment, and other symptoms [6].
• Rett syndrome, an X-linked dominant disorder caused by MECP2 mutations, and Angelman syndrome, an imprinted disorder caused by maternal 15q11-q13 or UBE3A deficiency, have phenotypic and genetic overlap with autism [7].
• These data suggest that a moderate increase in circulating melatonin levels significantly reduces motor activity during the sleep period in Angelman syndrome children, and promotes sleep [8].

High impact information on Angelman Syndrome

• A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome [9].
• Imprinting of the Angelman syndrome gene, UBE3A, is restricted to brain [10].
• Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons [11].
• The human P gene corresponds to the D15S12 locus within the chromosome segment 15q11-q13, which is typically deleted in patients with Prader-Willi and Angelman syndrome (see ref. 5 for review) [12].
• Familial Angelman syndrome caused by imprinted submicroscopic deletion encompassing GABAA receptor beta 3-subunit gene [13].

Chemical compound and disease context of Angelman Syndrome

• High-dose ethosuximide for epilepsy in Angelman syndrome: implication of GABA(A) receptor subunit [14].
• Pharmacologic evidence for abnormal thalamocortical functioning in GABA receptor beta3 subunit-deficient mice, a model of Angelman syndrome [15].
• Adverse effects of vigabatrin in Angelman syndrome [16].
• Decrease in benzodiazepine receptor binding in a patient with Angelman syndrome detected by iodine-123 iomazenil and single-photon emission tomography [17].
• Effects of a low dose of melatonin on sleep in children with Angelman syndrome [8].

Biological context of Angelman Syndrome

• Genomic inversions of human chromosome 15q11-q13 in mothers of Angelman syndrome patients with class II (BP2/3) deletions [18].
• The loss of the single gene, gabrb3, in these mice is sufficient to cause phenotypic traits that have marked similarities to the clinical features of AS, indicating that impaired expression of the GABRB3 gene in humans probably contributes to the overall phenotype of Angelman syndrome [19].
• The first is a familial case of Angelman syndrome in which the two affected children have mutations which affect the imprinting mechanism, as shown by the presence of paternal DNA methylation patterns at D15S63 and SNRPN and biparental inheritance of 15q11-q13 markers [20].
• Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families [21].
• Two human genetic disorders, Prader-Willi syndrome (PWS, MIM 176270) and Angelman syndrome (AS, MIM 105830), result from rearrangements of chromosome 15q11-q13, an imprinted region of the human genome [22].

Gene context of Angelman Syndrome

• As is the case with SNRPN, PWS patients with 15q11-q13 deletions do not express IPW, whereas expression is normal in Angelman syndrome patients [23].
• Mutations in NIPA1 (Nonimprinted in Prader-Willi/Angelman syndrome 1) have recently been identified as a cause of autosomal dominant pure HSP, with one mutation described in two unrelated families [24].
• The human gene for the poly(A)-specific ribonuclease (PARN) maps to 16p13 and has a truncated copy in the Prader-Willi/Angelman syndrome region on 15q11-->q13 [25].
• Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region [26].
• These data suggest that, like the candidate Angelman syndrome gene Ube3a (ubiquitin ligase), Usp29 may represent another imprinted gene involved in the ubiquitination pathway [27].

Analytical, diagnostic and therapeutic context of Angelman Syndrome

• Microarray analysis of gene/transcript expression in Angelman syndrome: deletion versus UPD [28].
• We have evaluated fluorescence in situ hybridization (FISH) analysis for the clinical laboratory detection of the 15q11-q13 deletion seen in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) using probes for loci D15S11, SNRPN, D15S10, and GABRB3 [29].
• We conclude that epilepsy was present in nearly all of our cases with Angelman syndrome, and that the EEG can be a useful diagnostic tool [30].

References