Genetic disorder causing severe developmental delay, seizures, frequent laughter, and ataxia (poor control of voluntary muscle movements).
Results from the non-expression of the Ube3A gene on chromosome 15.
Genetic Basis
Ube3A Gene: Stands for ubiquitin protein ligase E3A.
Codes for E6-associated protein.
E6-associated protein tags proteins with ubiquitin, leading to their degradation by the proteosome.
Chromosome 15 region around Ube3A is imprinted.
Gene Imprinting
Imprinting: Gene expression depends on the parent of origin.
Normally, only maternally derived Ube3A is expressed in the brain; the paternal copy is silenced.
Pathogenesis
If the maternal copy of Ube3A is compromised, Angelman Syndrome results.
Causes of Angelman Syndrome
Deletion: Most common cause.
Deletion of DNA on the maternal chromosome 15 including Ube3A.
May include the OCA2 gene, affecting pigmentation (light complexion).
Mutation: Mutation in maternal Ube3A leading to ineffective protein.
Paternal Uniparental Disomy:
Absence of maternal chromosome 15, replaced by an extra paternal one.
Both Ube3A copies silenced.
Imprinting Defect:
Methylation of maternal chromosome 15 silences Ube3A.
May occur due to errors in egg development or mutations in imprinting centers.
Inheritance and Pedigrees
Most cases are sporadic (new mutations).
Epigenetic inheritance can affect disease transmission.
Mutations from the father are asymptomatic since the paternal copy is off.
Genes near Ube3A have opposite imprinting, leading to Prader-Willi Syndrome if paternal genes are lost.
Prader-Willi Syndrome
Results from loss of paternal genes near the Ube3A region.
Causes low muscle tone, poor feeding in infancy, and overeating, obesity, and low IQ later on.
Symptoms of Angelman Syndrome
Delayed development, especially in reaching milestones.
Lack of speech, unsteady walking (arms flexed, hands pronated).
Other features: seizures, sleep difficulties, small head size, fair complexion, scoliosis.
Generally happy, excitable demeanor with hand flapping movements.
Treatment
No cure available.
Symptoms are addressed individually (e.g., communication boards for absent speech).
Conclusion
Angelman Syndrome is an imprinting disorder linked to the compromised expression of the maternal Ube3A gene on chromosome 15, leading to a range of severe neurological and developmental issues.