Prader-Willi/Angelman Methylation & Copy Number Analysis (Sendout)

single page view

General Information

Lab Name
Lab Code
167
External Test Id
LAB1894
Description

Test Description: DNA methylation and deletion/duplication study of the Prader-Willi syndrome (PWS)/Angelman syndrome (AS) Critical Region of chromosome 15. If the methylation pattern is characteristic of only maternal inheritance (absence of the paternally-inherited critical region), this is diagnostic for PWS. If the methylation pattern is characteristic of only paternal inheritance (absence of the maternally-inherited critical region), this is diagnostic for AS. This combined assay will provide information regarding the genetic mechanism by which an abnormal methylation result arises, e.g. by deletion vs. another mechanism such as uniparental disomy (UPD) or an imprinting defect. This assay does not distinguish between UPD and an imprinting defect. Knowledge of the molecular class can inform risk for relatives. There is emerging evidence for genotype-phenotype correlations. Broadly, all genetic mechanisms that give rise to either PWS or AS are associated with a similar clinical presentation for that syndrome.

Copy number variants that include the 15q11.2 BP1 to BP3 or 4 regions are reported.

In addition, this assay can detect the PWS/AS critical region duplication that causes 15q11-q13 duplication syndrome (BP1 to BP3 or BP1 to BP4). Duplication of the maternal chromosome 15 is characterized by developmental delay, intellectual disability, hypotonia, and seizures. Copy number variants that are limited to the 15q11.2 BP1 to BP2 region are not reported.

If the methylation test is positive and a deletion is not detected by this assay, subsequent UPD 15 testing can distinguish between uniparental disomy and an imprinting defect.

11% of individuals with a clinical diagnosis of Angelman syndrome will have a pathogenic variant in the UBE3A gene. DNA sequencing of the UBE3A gene should be considered in individuals with a clinical diagnosis of Angelman syndrome but normal methylation studies. Sequencing of UBE3A is available from the Seattle Children’s Hospital Laboratory as a single gene assay or as part of a larger panel for Angelman syndrome and related disorders.

References
Forms & Requisitions
Synonyms
15q11-q13 Duplication Syndrome, Angelman Methylation Analysis and CNV Analysis, Angelman Syndrome, AS DNA, LAB1894, Prader Willi, Prader Willi Methylation Analysis and CNV Analysis, Prader-Willi, PWS DNA

Interpretation

Method

Methylation-specific assay of the SNRPN and MAGEL2 alleles and deletion/duplication analysis of the 15q11.2-q13.1 loci, which contains the Prader-Willi/Angelman critical region (SALSA MLPA probemix ME028; MRC-Holland).

Ref. Range Notes

An interpretive report will be provided.

Interferences and Limitations

Limitations: 99% of cases of Prader-Willi detect and ~78% of cases of Angelman syndrome syndrome will be diagnosed by this method. 11% of individuals with a clinical diagnosis of Angelman syndrome will have a pathogenic variant in the UBE3A gene. UBE3A gene sequencing may be considered for individuals with a clinical diagnosis of Angelman syndrome but normal methylation studies.

This assay cannot provide detailed information regarding the size of a copy number change, but it can distinguish between type I (larger class, BP1-BP3) and type II (smaller class, BP2-BP3) copy number changes. Copy number variants that are limited to the BP1 to BP2 region of 15q11.2 are not reported.

Note: For patients who have had a whole blood transfusion, wait 10 days post transfusion to draw for genetic testing. No wait time is necessary for blood or saliva collection if the patient received leuko-reduced red cells or plasma.

References

Ordering & Collection

Specimen Type
Blood
Collection

Blood: 3 mL blood in LAVENDER TOP (EDTA) tube

  • Unacceptable: Heparin tubes

DNA: Extracted DNA from EDTA blood may be accepted at the discretion of the laboratory director. Please contact the laboratory genetic counselors at LabGC@seattlechildrens.org prior to sending extracted DNA.

  • Volume: 5µg DNA
    • Isolation of nucleic acids for clinical testing must be performed in a CLIA-certified
      laboratory or a laboratory meeting equivalent requirements as determined by the CAP
      and/or the CMS. DNA concentration minimum 100 µg/mL; 260/280 ratio 1.70-2.00.
Forms & Requisitions
Handling Instructions

Outside Laboratories:

  • Refrigerate blood samples until ready to ship. Transport at room temperature via overnight shipping.
  • Include a completed SCHL Molecular Genetics Laboratory requisition with the order.

Stability (Whole Blood): Ambient: 3-5 days; Refrigerated: 7 days; Frozen: Unacceptable.

Quantity
requested: 3 mL EDTA whole blood
minimum: 1 mL EDTA whole blood

Processing

Processing

Store at ambient temperature if sample will be sent same-day; otherwise store refrigerated until ready to transport.

Login: GSEND1-;REFRIG

  • GSNDT1: SCHL
  • GSTYP1: WB
  • GTSRQ1: ;Prader Willi Angelman Syndrome, Methylation & CNV (SCHL Test LAB1894)

Sendouts:

  • Order SCHL Test: LAB1894.
  • Send samples at ambient temperature with a completed SCHL Genetics requisition via DLMP or Delivery Express courier. If shipment is delayed, refrigerate sample until ready to send.

Stability (Whole Blood): Ambient: 3-5 days; Refrigerated: 7 days; Frozen: Unacceptable.

  • Note: Whole blood samples >7 days old may still be submitted to SCHL to be assessed for acceptability.

Stability (Extracted DNA): Ambient: Acceptable; Refrigerated: Acceptable; Frozen: Acceptable.

Performance

LIS Dept Code
Performing Location(s)
Sendout Seattle Children's Hospital Department of Laboratories
206-987-2617

4800 Sand Point Way NE
OC.8.720
Seattle, WA 98105
Frequency
Performed: Monday - Friday. Turnaround Time: 2-3 weeks.
Available STAT?
No

Billing & Coding

CPT codes
Billing Comments

CPT: 81331

LOINC