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Test Code PWS + AS DNA Prader-Willi/Angelman Methylation Analysis

Important Note

This one test can be ordered to evaluate both Prader-Willi and Angelman syndrome; Prader-Willi syndrome only; Angelman syndrome only

Additional Codes

PWS DNA

AS DNA

Clinical System Name

Prader Willi + Angelman Methylation Analysis

Angelman Methylation Analysis

Prader Willi Methylation Analysis

Description

DNA methylation study of the PWS/AS Critical Region of chromosome 15. If the methylation pattern is characteristic of maternal inheritance (absence of the paternally-inherited critical region), this is diagnostic for Prader-Willi syndrome. If the methylation pattern is characteristic of paternal inheritance (absence of the maternally-inherited critical region), this is diagnostic for Angelman syndrome.  

 

The same assay is performed to detect the maternally and paternally derived copies of the SNRPN alleles; if there is a strong clinical suspicion of either Prader-Willi or Angelman syndrome, it can be indicated by selecting the unique orderable for that disorder (PWS DNA or AS DNA).  If the clinical findings do not strongly support one over the other, the general orderable can be used (PWS + AS DNA).

 

Indications for Prader-Willi testing:  Indications for Angelman testing: 
Neonatal hypotonia & feeding difficulties Developmental delay, intellectual disability
Persistent hypotonia Seizures
History of poor suck Expressive speech impairment
Developmental delay Ataxia
History of above, plus excessive eating Inappropriate happy demeanor, hand flapping

  

Sample Requirements

Specimen: Whole blood, cord blood

Container(s): Lavender/EDTA, Yellow/ACD A or B

Preferred Vol: 3 mL

Minimum Vol: 1 mL

 

Note: Heparin samples (Green tops) are UNACCEPTABLE.

 

Specimen: Extracted DNA

Minimum: 10µg

Note: DNA concentration minimum 50 µg/mL; 260/280 ratio 1.70-2.00

  

Specimen: Cultured cells

Acceptable:  Fibroblasts

Container(s): T-25 flasks

Preferred Vol: 2 flasks

Processing Instructions

Reject due to: Heparin

Spin: No

Aliquot: No

Temp: Refrigerate

Storage location: Molecular Genetics box in CPA refrigerator #2

 

Off-site collection: Refrigerate blood samples until ready to ship.  Transport all sample types at room temperature via overnight shipping.

Stability

Specimen Type Temperature Time
Cultured cells Room temp 3 days
Whole blood, extracted DNA Room temp 3-5 days
Whole blood, extracted DNA Refrigerated 7 days
Extracted DNA Frozen ok

 

Note: Whole blood samples > 7days may be submitted to be assessed by our lab for acceptability for testing.

Availability

STAT Performed TAT
Contact lab Monday - Friday 2-3 weeks

 

Performing Laboratory

Seattle Children's Laboratory

Department

Department:  Molecular Genetics Laboratory

Phone: 206-987-3872

 

Lab Client Services: 206-987-2617

 

Lab Genetic Counselor: LabGC@seattlechildrens.org

Reference Range

Interpretive report will be provided

Methodology

Method: Methylation-specific PCR assay of SNRPN alleles.

 

Limitations: 99% of cases of Prader-Willi syndrome will be diagnosed by DNA methylation studies.  DNA methylation studies will detect ~78% of cases of Angelman syndrome. 11% of individuals with a clinical diagnosis of Angelman syndrome will have an imprinting defect caused by mutations in the UBE3A gene. Individuals with a clinical diagnosis of Angelman syndrome but normal methylation studies should have DNA sequencing of the UBE3A gene.

CPT Codes

81331 (updated 2/2/16 by jconta)

Special Instructions

If the methylation test is positive, a FISH (fluorescence in situ hybridization) test can be utilized to distinguish between uniparental disomy and a deletion. 


11% of individuals with a clinical diagnosis of Angelman syndrome will have an imprinting defect caused by mutations in the UBE3A gene. Individuals with a clinical diagnosis of Angelman syndrome but normal methylation studies should have DNA sequencing of the UBE3A gene.

 

Links to: Prader-Willi Syndrome GeneReviewAngelman Syndrome GeneReview

Requisition

Molecular Genetics

Clinical Utility

Prader-Willi syndrome is associated with neonatal hypotonia and feeding difficulties, changing to excessive eating later in infancy and childhood. Motor, cognitive, and language development are typically delayed. Prader-Willi syndrome is caused by the absence of the paternally-inherited criticial region of chromosome 15.

 

Angelman syndrome is associated with ataxia, seizures, absence of speech, hyperactivity, hypopigmentation, and severe mental retardation, and is caused by absence of the maternally-inherited criticial region of chromosome 15.

For diagnosis, DNA methylation study of the PWS/AS Critical Region is the recommended method. If the methylation pattern is characteristic of maternal inheritance, this is diagnostic for Prader-Willi syndrome. Maternal inheritance of the PWS/AS critical region can be caused by deletions of the paternal allele, receiving two copies of chromosome 15 from the mother (uniparental disomy) or defects in the imprinting process.  If the methylation pattern is characteristic of paternal inheritance, this is diagnostic for Angelman syndrome. Paternal inheritance of the PWS/AS critical region can be caused by deletions of the maternal allele, receiving two copies of chromosome 15 from the father (uniparental disomy) or defects in the imprinting process.