An Analysis of Phenotype and Genotype in a Large Cohort of Chinese Children with Angelman Syndrome

Genes (Basel). 2022 Aug 14;13(8):1447. doi: 10.3390/genes13081447.


Angelman syndrome (AS) is a neurodevelopmental genetic disorder, but there has been limited analysis of a large cohort of Chinese children with Angelman syndrome. This study aims to assess the phenotype and genotype of Chinese children with Angelman syndrome. We retrospectively analyzed data through a detailed online survey combined with an on-site study. Furthermore, phenotype analysis stratified by deletion and non-deletion groups was carried out. The responses of family members of 695 individuals with AS revealed that 577 patients (83.02%) had maternal deletions, 65 patients (9.35%) carried UBE3A mutations, 31 (4.46%) patients had UPD15pat (one patient with UPD15pat constituted by a mosaic), 10 patients (1.44%) had imprinting defects and 12 (1.58%) patients only showed abnormal methylation without further detection. We identified 50 different pathogenic variants in this cohort, although 18 of these variants were unreported. Recurrent variant c.2507_2510del (p.K836Rfs*4) was found in 7 patients. In the deletion group, patients were diagnosed at an earlier age, had a more severe clinical phenotype, a higher rate of epilepsy with more multiple seizure types, and more frequently combined medication. Strabismus and sleep disturbances were both common in deletion and non-deletion groups. The top three resources invested in caring for AS children are: daily involvement in patient care, rehabilitation cost, and anti-epileptic treatment. Our study showed the genetic composition of Chinese children with 83.02% of maternal deletions, and the mutation spectrum for UBE3A variants was expanded. Developmental outcomes are associated with genotype, and this was confirmed by deletion patients having a worse clinical phenotype and complex epilepsy.

Keywords: 15q deletion; Angelman syndrome; Chinese children; UBE3A; phenotype and genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelman Syndrome* / genetics
  • China
  • Epilepsy*
  • Genotype
  • Humans
  • Phenotype
  • Retrospective Studies

Grants and funding

The study was supported by grants from: Shanghai Key Laboratory of Birth Defects, Shanghai, 201102, China (Grant No.13DZ2260600); Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01); Supported by Shanghai Municipal Science and Technology Major Project (Grant No. 2018SHZDZX01) and ZJLab; Guangdong Key Project in “Development of new tools for diagnosis and treatment of Autism” (Grant No. 2018B030335001).