Test Catalog

Test Id : PWAS

Prader-Willi/Angelman Syndrome, Molecular Analysis, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirmation of diagnosis in patients suspected of having either Prader-Willi syndrome (PWS) or Angelman syndrome (AS) based on clinical assessment or previous laboratory analysis

 

Prenatal diagnosis in families at risk for PWS or AS

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Preferred first-tier test for diagnosis of Angelman syndrome (AS) and Prader-Willi syndrome (PWS). Multiplex ligation probe amplification (MLPA) is used to identify abnormal methylation of the PWS/AS region of chromosome 15.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
CULAF Amniotic Fluid Culture/Genetic Test Yes No
MATCC Maternal Cell Contamination, B Yes No
CULFB Fibroblast Culture for Genetic Test Yes No
_STR1 Comp Analysis using STR (Bill only) No, (Bill only) No
_STR2 Add'l comp analysis w/STR (Bill Only) No, (Bill only) No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge. For any prenatal specimen that is received, maternal cell contamination studies will be added.

 

See Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Multiple Ligation-Dependent Probe Amplification (MLPA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Prader Willi/Angelman Mol Analysis

Aliases
Lists additional common names for a test, as an aid in searching

Angelman Syndrome, Uniparental Disomy and Deletions

Methylation Studies

PWDNA

Prader-Willi Syndrome, Uniparental Disomy and Deletions

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge. For any prenatal specimen that is received, maternal cell contamination studies will be added.

 

See Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis

Specimen Type
Describes the specimen type validated for testing

Varies

Additional Testing Requirements

Mayo Clinic Laboratories highly recommends that this test be ordered along with a routine chromosomal microarray analysis, CMACB / Chromosomal Microarray, Congenital, Blood, if the diagnosis of Prader-Willi syndrome (PWS) or Angelman syndrome (AS) is not certain and chromosome analysis has not already been done.

 

All prenatal specimens must be accompanied by a maternal blood specimen. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Prenatal Specimens

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing.

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL

Amniotic Fluid: 10 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirmation of diagnosis in patients suspected of having either Prader-Willi syndrome (PWS) or Angelman syndrome (AS) based on clinical assessment or previous laboratory analysis

 

Prenatal diagnosis in families at risk for PWS or AS

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Preferred first-tier test for diagnosis of Angelman syndrome (AS) and Prader-Willi syndrome (PWS). Multiplex ligation probe amplification (MLPA) is used to identify abnormal methylation of the PWS/AS region of chromosome 15.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added at an additional charge. For any prenatal specimen that is received, maternal cell contamination studies will be added.

 

See Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Prader-Willi syndrome (PWS) is a congenital disorder characterized by a biphasic clinical course. Neonates with PWS are hypotonic, have a weak cry, and are initially poor feeders that improve over time. In later infancy and childhood, individuals with PWS have global developmental delay, short stature, hypogonadism, small hands and feet, and marked hyperphagia leading to obesity. PWS is thought to be due to loss of function of paternally expressed genes, although specific genes have not yet been definitively implicated in the phenotype of PWS.

 

Etiology of Prader-Willi syndrome:

-Chromosome 15 deletion (15q11-13): approximately 70% to 75%

-Maternal uniparental disomy (UPD): 20% to 30%

-Imprinting defect: 1% to 5%

-Chromosome rearrangement: rare

 

The phenotype caused by paternal deletions of 15q11-13 and by maternal UPD are generally identical with the exception of relative hypopigmentation being more common in patients with deletion PWS.

 

Angelman syndrome (AS) is a nonprogressive congenital disorder characterized by more significant developmental delay and intellectual disability, ataxia, seizures, jerky arm movements, macrostomia, tongue thrusting, unprovoked laughter, brachycephaly, and virtual absence of speech. AS is due to loss of function of the maternally expressed gene UBE3A.

 

Etiology of Angelman syndrome:

-Chromosome 15 deletion (15q11-13): approximately 70% to 75%

-Paternal UPD: approximately 5%

-UBE3A variant: approximately 10%

-Imprinting defect: 2% to 5%

-Chromosome rearrangement: rare

-Unknown: approximately 10%

 

The phenotype of AS patients with maternal deletions is generally more severe than that associated with paternal UPD or imprinting defects, including a higher rate or severity of microcephaly, seizures, and motor difficulties. Patients with AS caused by paternal UPD or imprinting defects generally show better growth and higher developmental and language abilities.

 

Both chromosome 15 deletions and UPD most often occur as de novo events during conception, and, thus, recurrence risk to siblings is very low. In rare cases, chromosome 15 deletions and UPD occur as a result of parental translocations or other rare cytogenetic rearrangements, and, in these cases, recurrence risks to siblings are increased.

 

The recurrence risk associated with imprinting defects is dependent on whether there is an identifiable variant.

 

UBE3A variants can occur sporadically or be inherited in an autosomal dominant fashion. There is a 50% recurrence risk to siblings in cases of an inherited UBE3A variant.

 

Due to the complex genetic etiology of PWS and AS and the corresponding variability in recurrence risks, careful cytogenetic and molecular testing and family assessment are necessary to provide accurate genetic counseling.

 

Initial studies to rule-out PWS or AS should include chromosomal microarray analysis to identify chromosome abnormalities that may have phenotypic overlap with PWS or AS, and methylation-sensitive multiple ligation-dependent probe amplification (MLPA) to identify deletions, duplications, and methylation defects. In cases where methylation-sensitive MLPA suggests either deletion or duplication, fluorescence in situ hybridization (FISH) can be used to confirm type I and type II deletions or characterize the disease mechanism, respectively. In cases where methylation-sensitive MLPA suggests abnormal methylation in the absence of a deletion or duplication, UPD studies can be used to characterize the disease mechanism.

 

Assessment of patients found to have a deletion in the PWS/AS critical region on routine cytogenetic analysis or chromosomal microarray can include confirmation of the deletion by FISH analysis and MLPA analysis to define parent of origin.

 

For more information, see Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

In addition to disease-related probes, the multiple ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

 

Rare variants (ie, polymorphisms) exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.

 

Methylation status cannot be assessed on chorionic villus specimens.

 

Rare cases of Prader-Willi syndrome or Angelman syndrome (AS) result from a subtle balanced translocation inherited from one of the parents. These may not be detected by this assay.

 

A negative molecular test result, especially in the case of a clinical suspicion of AS, does not rule out the diagnosis, because point alterations may not be detected by these methods.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Buiting K: Prader-Willi syndrome and Angelman syndrome. Am J Med Genet C Semin Med Genet. 2010 Aug 15;154C(3):365-376

2. Williams CA, Beaudet AL, Clayton-Smith J, et al: Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet A. 2006 Mar 1;140(5):413-418

3. Gunay-Aygun M, Schwartz S, Heeger S, O'Riordan MA, Cassidy SB: The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics. 2001 Nov;108(5):E92

4. Nygren AOH, Ameziane N, Duarte HMB, et al: Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acids Res. 2005 Aug 16;33(14):e128

5. Procter M, Chou LS, Tang W, Jama M, Mao R: Molecular diagnosis of Prader-Willi and Angelman syndromes by methylation-specific melting analysis and methylation-specific multiplex ligation-dependent probe amplification. Clin Chem. 2006 Jul;52(7):1276-1283

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Methylation-sensitive multiple ligation-dependent probe amplification is utilized to test for the presence of large deletions, duplications and methylation defects in the Prader-Willi/Angelman syndrome critical region.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

10 to 14 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available) Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81331-SNRPN/UBE3A, (small nuclear ribonucleoprotein polypeptide Nand ubiquitin protein ligase E3A) (eg, Prader-Willi syndrome and/or Angelman syndrome), methylation analysis

88235-Tissue culture for amniotic fluid (if appropriate)

88240-Cryopreservation (if appropriate)

81265-Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (eg, pre-transplant recipient and donor germline testing, post-transplant non-hematopoietic recipient germline [eg, buccal swab or other germline tissue sample] and donor testing, twin zygosity testing or maternal cell contamination of fetal cells (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PWAS Prader Willi/Angelman Mol Analysis 35466-2
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
52913 Result Summary 50397-9
52914 Result 82939-0
52915 Interpretation 69047-9
52916 Reason for Referral 42349-1
52917 Specimen 31208-2
52918 Source 31208-2
52919 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports