Molecular and clinical characterization of Angelman syndrome in Chinese patients

Abstract

Angelman syndrome (AS) is a neurobehavioral disorder caused by lack of function of the maternal copy of the ubiquitin-protein ligase E3A (UBE3A) gene. In our study, 49 unrelated patients with classic AS phenotypes were confirmed by methylation-specific PCR (MS-PCR) analysis, short tandem repeat linkage analysis, and mutation screening of the UBE3A gene. Among the Chinese AS patients, 83.7% (41/49) had deletions on maternal chromosome 15q11.2-13. Paternal uniparental disomy, imprinting defects, and UBE3A gene mutations each accounted for 4.1% (2/49). Two AS patients were confirmed by MS-PCR analysis, but the pathogenic mechanism was unknown because their parents' samples were unavailable. Of the two described UBE3A gene mutations, that is, p.Pro400His (c.1199C>A) and p.Asp563Gly (c.1688A>G), the latter has not been reported previously. Mutation transmission analysis showed that the p.Pro400His and p.Asp563Gly mutations originated from asymptomatic mothers. The patients with the maternal deletion showed AS clinical manifestations that were consistent with other studies. However, the incidence of microcephaly (36.7%, 11/30) was lower than that in the Caucasian population (approximately 80%), but similar to that of the Japanese population (34.5%). Our study demonstrated that the occurrence of microcephaly in AS may vary among different populations.

Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome

“…The ages of 5 AS patients at diagnosis were from 2 to 12 months. All AS patients (100%) showed seizures which were similar to that reported previously [ 19 ]. The apparent happy disposition, such as inappropriate laughter and excitability, was the other unique behavior of the AS patients and noticeable for pediatricians to suspect that child had AS and suggest further genetic tests.…”

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

“…Epilepsy and ataxia were present in almost all microdeletion type AS patient in recent studies of China and Japan (Saitoh et al, 1994;Bai et al, 2014) and microcephaly was present in half of them. In our study, the prevalence of microcephaly was similar while the epilepsy and ataxia developed in 77.8% of our deletion type case.…”

Atypical Angelman syndrome due to a mosaic imprinting defect: Case reports and review of the literature

“…In contrast, those with unparental disomy, an imprinting defect or mosaic AS tend to have a milder phenotype. These variable AS phenotypes are summarized in Table [Varela et al, ; Tan et al, ; Horváth et al, ; Bai et al, , Luk and Lo, ]. Importantly, the phenotype of individuals with mosaic AS may not be entirely consistent with the diagnostic features recommended by the 2005 Consensus Statement of the United States AS Foundation [Williams et al, ].…”