Angelman Syndrome Revisited

Paprocka, Justyna; Jamroz, Ewa; Szwed-Białozyt, Barbara; Jezela‐Stanek, Aleksandra; Kopyta, Ilona; Marszał, Elżbieta

doi:10.1097/01.nrl.0000253067.32759.aa

Cited by 18 publications

(12 citation statements)

References 35 publications

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“…Behavioral data from mice with a maternal Ube3a to Gabrb3 deletion are mostly consistent with previous studies of Ube3a mutant mice, but the current study is more extensive as summarized in Table 1 [23], [25], [66]. Although mutations in the UBE3A gene cause typical AS in humans, it has been reported in some studies that the phenotypes such as seizures in AS patients with UBE3A mutations are milder than in AS patients with large deletions of 15q11–q13 [20], [21], [22]. In mice, we noticed that the frequency of observed seizure activity was not significantly different between deletion and Ube3a mutation mice [23].…”

Section: Discussionsupporting

confidence: 89%

“…In addition, there were early reports suggesting that loss-of-function UBE3A mutations, paternal UPD of chromosome 15, or imprinting mutations in AS were associated with relatively milder epilepsy while AS patients with a deletion of chromosome 15q11–13 had more severe epilepsy [20]. However, other studies found no genotype-phenotype correlation for EEG abnormalities and epilepsy among AS patients with different genotypes [21], [22]. One caveat of these studies was the relative small sample size which might bias the results and conclusion.…”

Section: Introductionmentioning

confidence: 99%

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Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3

et al. 2010

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Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11–q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11–q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m−/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m−/p+), but not paternal (m+/p−), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3

et al. 2010

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“…For genotype-phenotype correlation, it was well reported that deletion type AS had poor neurological outcome in term of intellectual disability, microcephaly and epilepsy Paprocka et al, 2007) as compared with non-microdeletion type.…”

Section: Discussionmentioning

confidence: 99%

Angelman syndrome in Hong Kong Chinese: A 20 years’ experience

Luk

2016

European Journal of Medical Genetics

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“…It is typically considered a generalized epilepsy, with atypical absence, atonic, generalized tonic-clonic, and myoclonic the most frequent seizure types, but complex partial seizures have also been reported in 13-39% of those with epilepsy (Casara et al, 1995;Buoni et al, 1999;Nolt et al, 2003;Ohtsuka et al, 2005;Valente et al, 2005Valente et al, , 2006, including seizures with occipital lobe semiology consisting of eye deviation and vomiting (Viani et al, 1995). Sporadic cases of infantile spasms have been reported as well (Galvan-Manso et al, 2005a, 2005bUemura et al, 2005;Paprocka et al, 2007). Nonconvulsive status epilepticus (NCSE) is common (Pelc et al, 2008), but reports on the prevalence of both convulsive status epilepticus and NCSE are variable, with reported rates of NCSE as high as 91% (Ohtsuka et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Epilepsy in Angelman syndrome: A questionnaire‐based assessment of the natural history and current treatment options

et al. 2009

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This is the largest study to date assessing epilepsy in AS. Although epilepsy in AS is considered a generalized epilepsy, there was a high prevalence of partial seizures. There are few previous data regarding the use of newer AED in AS, and the results of this study suggest that these newer agents, specifically levetiracetam and lamotrigine, may have efficacy similar to that of valproic acid and clonazepam, and that they appear to have similar or better side-effect profiles. Nonpharmacologic therapies such as dietary therapy and vagus nerve stimulation (VNS) also suggest favorable efficacy and tolerability, although further studies are needed.

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Angelman Syndrome Revisited

Cited by 18 publications

References 35 publications

Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3

Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3

Angelman syndrome in Hong Kong Chinese: A 20 years’ experience

Epilepsy in Angelman syndrome: A questionnaire‐based assessment of the natural history and current treatment options

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