Angelman Syndrome

Definition

Angelman syndrome is a neurodevelopmental disorder characterized by severe intellectual disability, developmental delays, speech impairment, and distinct behavioral features such as a happy demeanor and frequent laughter. This condition is often linked to abnormalities in the UBE3A gene, which is subject to epigenetic regulation through processes such as DNA methylation, leading to the loss of expression of this critical gene in neurons.

5 Must Know Facts For Your Next Test

1. Angelman syndrome is primarily caused by deletions or mutations in the UBE3A gene on chromosome 15 inherited from the mother, while the paternal allele is usually inactive in neurons due to genomic imprinting.
2. Patients with Angelman syndrome often exhibit additional features such as seizures, ataxia (problems with coordination), and sleep disturbances, all contributing to their overall developmental challenges.
3. The distinctive behavioral traits of individuals with Angelman syndrome include an overly cheerful demeanor, frequent laughter, and hand-flapping movements, which are often misinterpreted as happiness or excitement.
4. Current research is exploring potential therapies that target the epigenetic mechanisms involved in Angelman syndrome, including strategies to activate the silent paternal UBE3A allele to restore its function.
5. Early diagnosis and intervention are critical for improving outcomes for children with Angelman syndrome, with therapies often focusing on speech, motor skills, and behavior management.

Review Questions

• How does the loss of expression of the UBE3A gene contribute to the symptoms observed in Angelman syndrome?
  • The loss of expression of the UBE3A gene is central to the development of Angelman syndrome because this gene plays a critical role in synaptic function and neural development. In individuals with this condition, mutations or deletions typically affect the maternal copy of UBE3A while leaving the paternal copy inactive due to genomic imprinting. As a result, neurons do not express UBE3A, leading to impaired neural connectivity and function, which manifest as intellectual disabilities and other neurodevelopmental symptoms.
• Discuss how DNA methylation and genomic imprinting are involved in the regulation of the UBE3A gene in Angelman syndrome.
  • DNA methylation and genomic imprinting are crucial in regulating the expression of the UBE3A gene. In normal development, the UBE3A gene is expressed from the maternal allele while the paternal allele is silenced by DNA methylation in neurons. In Angelman syndrome, deletion or mutation of the maternal UBE3A leads to a complete lack of its expression since the paternal allele remains silenced. This epigenetic regulation highlights how alterations in DNA methylation patterns can lead to significant clinical outcomes.
• Evaluate potential therapeutic strategies being researched for Angelman syndrome that target its epigenetic basis.
  • Research into therapeutic strategies for Angelman syndrome is focusing on reversing the effects of imprinting and reactivating the paternal UBE3A allele. Approaches include using small molecules that inhibit DNA methyltransferases to demethylate regions controlling UBE3A expression or employing CRISPR/Cas9 technology for precise editing. Additionally, gene therapy techniques aim to deliver functional copies of UBE3A directly into affected neurons. These potential therapies reflect an understanding of the epigenetic mechanisms at play and offer hope for more effective treatments for those affected by this condition.

Related terms

UBE3A: A gene that encodes an E3 ubiquitin ligase protein involved in protein degradation and synaptic function; mutations or deletions of this gene are central to Angelman syndrome.

Imprinting: An epigenetic phenomenon where genes are expressed in a parent-of-origin-specific manner, which plays a crucial role in the manifestation of Angelman syndrome due to the loss of paternal allele expression.

DNA Methylation: A biochemical process involving the addition of a methyl group to the DNA molecule, often affecting gene expression; altered DNA methylation patterns are implicated in the regulation of genes associated with Angelman syndrome.