Angelman/Prader-Willi - MLPA Analysis
Definition
Angelman syndrome results from loss of function of the maternal copy of the UBE3A gene, of which normally only the maternally derived allele is expressed in the brain; it is a neurodevelopmental disorder characterized by severe developmental delay, speech impairment, gait ataxia and frequent laughter. It can arise through four mechanisms: 15q11.2-q13 deletion (65-75%), paternal uniparental disomy (3-7%), imprinting defect (3%) and direct UBE3A mutations (11%). Prader-Willi syndrome, by contrast, results from the absence of the paternal (father-derived) contribution in the same region and presents with severe hypotonia and feeding difficulties in early infancy, followed by excessive appetite in early childhood and progression to morbid obesity; paternal deletion (60-70%), maternal UPD (30-40%) or imprinting defects (2-4%) are responsible. Methylation-sensitive MLPA evaluates copy number and methylation status in this region together and aids the diagnosis of both syndromes.
Gene/region analyzed
15q11 - Deletion/Duplication
Method
MLPA Analysis
Accepted sample types
EDTA blood, AF, CVS
Inheritance
In both syndromes the parent of origin of the loss is decisive: Angelman arises from loss of maternal function and Prader-Willi from loss of paternal function. Most cases are de novo and the recurrence risk is below 1%; however, in families carrying an inherited UBE3A variant or an imprinting center deletion the risk can be as high as 50%.