Learning Objective: At the end of this lesson, the learner will be able to describe the principles of genomic imprinting, identify key imprinting disorders, and recognize their clinical features and parent-of-origin patterns.
Principle of Genomic Imprinting
- One gene copy is silenced by methylation, so only the other allele is expressed.
- Parent-of-origin effect: The expressed allele may be mutated, deleted, or not expressed, causing disease.
High-Yield Imprinting Disorders
| Syndrome | Gene Silenced | Mutation / Deletion | Chromosome | Clinical Features | Notes / Mnemonic |
|---|---|---|---|---|---|
| Prader-Willi syndrome (PWS) | Maternal alleles silenced | Paternal allele deleted or mutated | Chromosome 15q11-q13 | Hyperphagia, obesity, intellectual disability, hypotonia, hypogonadism | POP → Paternal deletion, Obesity, Prader-Willi |
| Angelman syndrome (AS) | Paternal UBE3A silenced | Maternal allele deleted or mutated | Chromosome 15q11-q13 | Severe intellectual disability, ataxia, seizures, inappropriate laughter, hand-flapping | MAMAS → Maternal deletion, Angelman, Mood/Ataxia, Seizures |
Additional Notes:
- 25% of PWS cases are due to maternal uniparental disomy.
- 5% of AS cases are due to paternal uniparental disomy.
- Mnemonic: “Hails the Angels” → helps remember Angelman features.
High-Yield Tips
- Prader-Willi → paternal deletion expressed, maternal copy silenced → obesity, hypotonia, hypogonadism.
- Angelman → maternal deletion expressed, paternal UBE3A silenced → ataxia, seizures, inappropriate laughter.
- Both involve chromosome 15, but the parent-of-origin determines phenotype.
