Molecular Genetics Angelman Syndrome, UBE3A Sequencing

Angelman syndrome is a disorder characterized by severe developmental delay, a happy demeanor, limited speech and language, as well as abnormal gait and movement. This disorder is found in approximately 1 in 15,000 individuals, however it may be underdiagnosed as most of the clinical features do not manifest until 1 year of age or later. Molecular defects leading to Angelman syndrome involve absence or inactivation of the maternally inherited UBE3A allele and include abnormal DNA methylation, large deletions of the Angelman/Prader-Willi regulatory region, uniparental disomy, deletions of the Angelman syndrome imprinting control regions, as well as mutations in UBE3A. Approximately 70% of molecular defects in Angelman syndrome are large deletions of 15q11.2-q13, uniparental disomy or deletions of the Angelman syndrome imprinting control region (approximately 10%), and no molecular defects are found in approximately 10% of individuals. Mutations in UBE3A cause approximately 10% of Angelman syndrome cases.

Reasons for Referral:

• Suspected Angelman syndrome diagnosis with normal DNA methylation results
• Carrier testing for relatives with an affected Angelman syndrome family member
• Predispositional testing for asymptomatic children with an affected sibling or family member

For detailed information and ordering instructions, please refer to Full Gene Analysis (1240). Genes may be added or removed from the list below if clinically indicated.

Angelman syndrome testing includes the following gene(s):
UBE3A

1. Clayton-Smith, J et al. Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet 2003; 40: 87-95.
2. Tan, W et al. Angelman syndrome: Mutations Influence Features in Early Childhood. Am J Med Genet Part A 2010; 155: 81-90.
3. Williams, C et al. Clinical and genetic aspects of Angelman syndrome. Genetics in Medicine 2010; 12(7): 385-395.
4. Schneider M. et al, 2007 Clin Genet 72:30-38.