Diagnostic testing:
- Clinical suspicion of Angelman or Prader-Willi syndrome
Identify genetic mechanism:
- Analyze for UPD15 after Angelman or Prader-Willi confirmed by methylation-sensitive MLPA
Diagnostic testing:
This test assesses methylation status and copy gain/loss across the 15q11-q13 chromosomal region by methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA).
Identify genetic mechanism:
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by maternal (for PWS) or paternal (for AS) uniparental disomy of chromosome 15 in 20-25% and 3-7% of cases, respectively (PMID: 20459762). This test assesses uniparental disomy of chromosome 15 by genotyping of 13 polymorphic short tandem repeats (STRs, list available upon request). Biparental inheritance is assessed by genotyping of four STRs on chromosomes 13, 18, 21, and X.
Diagnostic testing :
MS-MLPA is performed using the ME028-D1 kit (MRC-Holland), as per practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes (PMID: 20459762).
Identify genetic mechanism:
STRs are genotyped by multiplex PCR and fluorescence-based fragment size analysis.
Diagnostic testing :
This test identifies alterations in more than 99% of individuals with Prader-Willi syndrome, and approximately 80% of individuals with Angelman syndrome (PMID: 20459762). A negative result does not rule out the possibility that the individual harbors a rare variant not detected by this assay, such as a mosaic alteration. Analysis is dependent on accurate clinical diagnosis of affected individuals and on correct reporting of family relationships. DNA variants located in primer and probe binding sites can result in inaccurate diagnosis.
Identify genetic mechanism:
Analysis is dependent on accurate clinical diagnosis of affected individuals and on correct reporting of ethnicity and family relationships. DNA variants located in primer binding sites and rare genotyping errors can result in inaccurate diagnosis.
Turnaround time: 4-6 weeks
Specimens accepted:
- 2 x 4 mL blood in EDTA tubes (purple top tube) – 2 mL for newborns
- DNA: min 10 ug
- Amniotic fluid: min 10 ml
- Direct CVS: min 10 mg direct villi
- Cultured amniocytes or CVS: 2 x T25 flasks (confluent)
- For any other sample type, contact the laboratory for testing availability
Submit your test request using our molecular genetics requisition.