General pathology · Genetic disease
Genomic imprinting: Prader–Willi and Angelman !
- Mechanism
Some genes work only when they come from the father and others only from the mother; losing the active copy causes disease even if the other is intact.
Updated 2026-11-01
What it is
Imprinting is an epigenetic mark, mainly DNA methylation, laid down in the gametes according to the parent's sex, which silences one allele in the child. At 15q11-q13, losing the paternal contribution causes Prader-Willi syndrome and losing the maternal one causes Angelman syndrome: the same deletion, opposite pictures.
Step by step
- During gamete formation old marks are erased and new ones set according to the parent's sex.
- At 15q11-q13 the maternal chromosome silences the Prader-Willi genes (such as SNRPN) by methylation.
- In neurons, the paternal chromosome silences UBE3A; only the maternal copy works.
- If the paternal region is lost (deletion, maternal disomy or imprinting defect), no Prader-Willi genes are active.
- If the maternal region or maternal UBE3A is lost, neurons have no UBE3A: Angelman syndrome.
- The marks persist in the child and are reset again in the child's own germ line.
Prader-Willi versus Angelman
| Feature | Prader-Willi | Angelman |
|---|---|---|
| Missing contribution | Paternal 15q11-q13 | Maternal (UBE3A gene) |
| Mechanisms | Paternal deletion, maternal disomy, imprinting defect | Maternal deletion, paternal disomy, UBE3A mutation, imprinting defect |
| Newborn | Marked hypotonia and weak suck | Usually looks normal at birth |
| Childhood and adulthood | Hyperphagia and obesity, short stature, small hands and feet, hypogonadism, mild to moderate intellectual disability | Severe intellectual disability, absent speech, ataxic gait, seizures, frequent laughter, microcephaly |
Clinical notes
- In Prader-Willi, obesity from hyperphagia is the main source of complications; controlling access to food is central.
- In Beckwith-Wiedemann, regular abdominal ultrasound is used to watch for embryonal tumours in childhood.
Test yourself
Think of the answer, then tap the question to see it.
What happens if a child inherits both chromosomes 15 from the mother?
Maternal uniparental disomy: no active paternal Prader-Willi genes, so the child develops Prader-Willi syndrome.
Which gene explains most of the neurological picture of Angelman syndrome?
UBE3A, which in neurons is expressed only from the maternal chromosome.
Which test detects deletion, disomy and imprinting defect in Prader-Willi?
DNA methylation analysis of the 15q11-q13 region.
Which tumours are screened for in Beckwith-Wiedemann syndrome?
Wilms tumour and hepatoblastoma, especially in the first years of life.
Related
- Nonclassic inheritance: repeat expansions, mitochondrial genes, imprinting, mosaicism
- Chromosome abnormalities: number and structure
- Tumours of infancy and childhood
Related conditions
- Prader–Willi and Angelman syndromes (imprinting)
- Beckwith–Wiedemann syndrome
- Wilms tumour (nephroblastoma)
- Obesity
- Neonatal hypoglycaemia (including infant of a diabetic mother)
- Male hypogonadism
Elsewhere in DurgiPedia
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: What are genomic imprinting and uniparental disomy?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Prader-Willi syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Angelman syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Beckwith-Wiedemann syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.