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Angelman Syndrome and Prader-Willi Syndrome by Methylation-Sensitive PCR, Fetal
2012232
Ordering Recommendation

Prenatal testing for Angelman syndrome or Prader-Willi syndrome. Identifies cases resulting from molecular mechanisms that produce abnormal methylation patterns.

Mnemonic
AS PWS FE
Methodology
Methylation Sensitive Polymerase Chain Reaction/Fluorescence Monitoring
Performed
Mon, Thu
Reported
2-7 days
New York DOH Approval Status
This test is New York DOH approved.
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
 
Collect
Fetal Specimen: Four (4) T-25 flasks at 80 percent confluency of cultured amniocytes. If the client is unable to culture amniocytes, this can be arranged by contacting ARUP Client Services at (800) 522-2787. Or amniotic fluid. 
AND Maternal Cell Contamination Specimen
: Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B). 
Specimen Preparation
Cultured Amniocytes: Fill flasks with culture media. Transport four (4) T-25 flasks at 80 percent confluency of cultured amniocytes. Backup cultures must be retained at the client's institution until testing is complete.
OR Amniotic Fluid
: Transport 20 mL unspun fluid. (Min: 10 mL)
AND Maternal Cell Contamination Specimen
: Transport 3 mL whole blood. (Min: 1 mL) 
Storage/Transport Temperature
Cultured Amniocytes: CRITICAL ROOM TEMPERATURE. Must be received within 48 hours of shipment due to liability of cells.
Amniotic fluid
: Room temperature.
Maternal Cell Contamination Specimen
: Room temperature. 
Unacceptable Conditions
 
Remarks
Maternal specimen is recommended for proper test interpretation. Order Maternal Cell Contamination. Patient History Form is available on the ARUP Web site or by contacting ARUP Client Services. 
Stability
Fetal Specimen: Ambient: 48 hours; Refrigerated: Unacceptable; Frozen: Unacceptable
Maternal Cell Contamination Specimen
: Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable 
Reference Interval
By report
Interpretive Data
Background information: Angelman Syndrome and Prader-Willi Syndrome by Methylation, Fetal:
Characteristics of Angelman Syndrome (AS):
Developmental delays by 6-12 months of age, seizures, microcephaly, movement or balance disorder, minimal or absent speech, and a distinctive behavioral phenotype, which includes a happy demeanor with frequent laughter, hand flapping, and excitability.
Prevalence
: 1 in 15,000.
Inheritance:
Varies, depending on the molecular genetic mechanism.
Cause
: Absence of maternal expression of the UBE3A gene.
Molecular Genetic Mechanisms
: Microdeletions in the AS/PWS critical region (68 percent), UBE3A mutations (11 percent), paternal uniparental disomy of chromosome 15 (7 percent), imprinting center defects (3 percent), unbalanced chromosome translocation (less than 1 percent), and unknown (10 percent).
Clinical Sensitivity:
78 percent.
Analytical Sensitivity and Specificity:
99 percent.
Methodology:
Bisulfite conversion and PCR amplification to detect methylation using melting curve analysis.
Limitations
: Molecular mechanisms not affecting methylation patterns that may result in AS will not be assessed. Diagnostic errors can occur due to rare sequence variations.

Characteristics of Prader-Willi Syndrome (PWS):
Neonatal hypotonia, hyperphagia, obesity, global developmental delay, mild intellectual disability, hypogonadism, and a distinctive behavioral phenotype, which includes temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive behavior.
Prevalence
: 1 in 15,000.
Inheritance:
Varies, depending on the molecular genetic mechanism.
Cause
: Absence of the paternally contributed PWS/AS critical region of chromosome 15q11.2-q13.
Molecular Genetic Mechanisms
: Microdeletions in the PWS/AS critical region (70-75 percent), maternal uniparental disomy of chromosome 15 (25-29 percent), imprinting center defect or balanced chromosome translocation (less than 1 percent).
Clinical Sensitivity:
Over 99 percent.
Analytical Sensitivity and Specificity:
99 percent.
Methodology:
Bisulfite conversion and PCR amplification to detect methylation using melting curve analysis.
Limitations
: Molecular mechanisms not affecting methylation patterns that may result in PWS will not be assessed. Diagnostic errors can occur due to rare sequence variations.

For quality assurance purposes, ARUP Laboratories will confirm the above result at no charge following delivery. Order Confirmation of Fetal Testing and include a copy of the original fetal report (or the mother's name and date of birth) with the test submission. Please contact an ARUP genetic counselor at (800) 242-2787 extension 2141 prior to specimen submission.

This test is performed pursuant to an agreement with Roche Molecular Systems, Inc.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
CPT Code(s)
81331; 81265 Fetal Cell Contamination (FCC)
Components
Component Test Code*Component Chart NameLOINC
0050548Maternal Contamination Study Fetal Spec31208-2
0050612Maternal Contam Study, Maternal Spec31208-2
2005079Angelman and Prader-Willi Result35466-2
2012226Angelman and Prader-Willi Fetal Specimen31208-2
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases