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Angelman/Prader-Willi Syndromes Methylation Assay

CPT:

81331


Synonyms

Prader-Willi and Angelman Syndromes, DNA Analysis; PWS Methylation Assay;


Test Includes

This assay detects all cases of AS and PWS arising from UPD, microdeletions and imprinting defects, but does not define the nature of underlying genetic defect. UBE3A mutations that cause AS are not detected by this assay.


Special Instructions

Please provide pertinent findings (family or personal) of intellectual disability, autistic behaviors, developmental delay, or obesity. It is recommended that in addition to this methylation-based testing, High-resolution Chromosome Analysis be ordered (052215) to distinguish between the underlying mechanisms.



Specimen Requirements


Volume

7 mL whole blood; 10 mL amniotic fluid; or LabCorp buccal swab kit


Minimum Volume

3 mL whole blood; 5 mL amniotic fluid; or two buccal swabs


Container

Lavender-top (EDTA) tube, yellow-top (ACD) tube, sterile plastic conical tube or two confluent T25 flasks for fetal testing, or LabCorp buccal swab kit


Storage Instructions

Maintain specimen at room temperature or refrigerate. Do not freeze.


Causes for Rejection

Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container; one buccal swab; wet buccal swab


Test Details


Use

This test detects all major causes of the Prader-Willi and Angelman syndrome


Limitations

Approximately 11% of Angelman syndrome cases arising from UBE3A mutations will not be detected by this test.


Methodology

Methylation-specific PCR and gel electrophoresis


Pregnancy Week

14–21 Weeks
22+ Weeks

Additional Information

Angelman syndrome (AS) (OMIM 105830) is characterized by severe developmental delay or intellectual disability, severe speech impairment, gait ataxia and/or jerking limb motions, and an inappropriate happy demeanor that includes frequent laughing, smiling, and excitability. Neonatal hypotonicity may also occur. Approximately 70% of AS patients have a deletion of 15q11-13 in the maternally-contributed chromosome 15, with about 3% to 5% of AS cases resulting from paternal uniparental disomy (UPD). Approximately 11% of AS cases result from mutations in the maternal copy of the UBE3A gene that also maps to 15q11-13. An abnormality of the imprinting process occurs in a portion of the remaining patients. Prader-Willi syndrome (PWS) (OMIM 176270) is caused by an abscess of paternal SNRPN gene expression. The disease is characterized by diminished fetal activity, severe postnatal hypotonia, failure to thrive in infancy followed by hyperphagia, obesity, developmental delay, and hypogonadism. PWS may result from a microdeletion of the paternal chromosome at 15q11-13 (70%), maternal UPD (25%), or from an imprinting defect. Imprinting defects may be associated with a 50% recurrence risk, however, the risk is negligible for cases involving microdeletions or UPD. Consequently, etiological testing may be indicated. All test results must be combined with clinical information for the most accurate interpretation.


References

Diagnostic testing for Prader-Willi and Angelman syndromes: Report of the ASHG/ACMG Test and Technology Transfer Committee. Am J Hum Genet. 1996 May; 58(5):1085-1088. PubMed 8651269

Glenn CC, Porter KA, Jong MT, Nicholls RD, Driscoll DJ. Functional imprinting and epigenetic modification of the human SNRPN gene. Hum Mol Genet. 1993 Dec; 2(12):2001-2005. PubMed 8111367

Kubota T, Das S, Christian SL, Baylin SB, Herman JG, Ledbetter DH. Methylation-specific PCR simplifies imprinting analysis. Nat Genet. 1997 May; 16(1):16-17. PubMed 9140389

Wevrick R, Francke U. Diagnostic test for the Prader-Willi syndrome by SNRPN expression in blood.Lancet. 1996 Oct 19; 348(9034):1068-1069. PubMed 8874459

Zeschnigk M, Lich C, Buiting K, Doerfler W, Horsthemke B. A single-tube PCR test for the diagnosis of Angelman and Prader-Willi syndrome based on allelic methylation differences at the SNRPN locus. Eur J Hum Genet. 1997 Mar-Apr; 5(2):94-98. PubMed 9195159

 


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