Clinical Background
Genetic Background
Genetic defect | Proportion of cases | Recurrence risk |
---|---|---|
De novo deletion of 15q11-q13 on the paternal chromosome | 75-80% | <1% |
Maternal uniparental disomy (UPD) of chromosome 15 | 20-25% | <1% |
Imprinting defects (with an imprinting centre deletion excluded) | ≈1% | <1% |
Imprinting centre deletion | ≈ 10-15% of patients with an imprinting defect | Up to 50% (if present in father) |
Genetic defect | Proportion of cases | Recurrence risk |
---|---|---|
De novo deletion of 15q11-q13 on the maternal chromosome | 70-75% | <1% |
Paternal uniparental disomy (UPD) of chromosome 15 | 3-7% | <1% |
Imprinting defect (with an imprinting centre deletion excluded) | 2-3% | <1% |
Deletions of the imprinting centre | ≈ 10-15% of patients with an imprinting defect | Up to 50% (if present in mother) |
UBE3A mutation | ≈10% | 50% if present in mother |
No identifiable molecular abnormality | ≈10% | Unknown (up to 50%) |
Methods
Results
Strategies for the analysis of PWS and AS
Molecular genetic testing methods
MS-PCR
Southern Blot Analysis
Alternative techniques
MS-MLPA
Microsatellite Analysis
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D15S113 (LS6-1/2). This is a CA repeat from within the critical region. The presence of null alleles (or non-amplification alleles) have been observed with this marker and can complicate the analysis of AS and PWS cases. Under certain conditions, a non-amplification allele can be misinterpreted as a small deletion. The frequency of these alleles in families without AS has been estimated to be around 4%. Alternative primers can be designed; however, this marker is best avoided.
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D15S817. The presence of three alleles has been observed with this marker with certain primer sets due to complex duplications in the region where the marker is located. Since there is a low frequency/density of useful markers for the more centromeric PWS/AS region, the use of the following primer pair (D15S817F, 5'-TGGAACCAATAGGATAGACAC-3' D15S817R, 5'-GGTCAGCCTCCATAATCA-3') can resolve this problem.