Prader-Willi Syndrome, Methylation Analysis

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Gene: SNRPN (imprinted), NDN

Chromosomal Locus: 15q11.2

Protein: Small nuclear ribonucleoprotein-associated protein N, Necdin

Pseudonyms: Prader-Labhart-Willi syndrome, PWS

TURNAROUND TIME: 15 days   

2012 AMA code: 81331

TESTING METHODOLOGY: Methylation analysis

SPECIMEN REQUIREMENTS:

  • Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
  • Min. Collection: 0.7 ml whole blood EDTA.
  • Transport: Blood in EDTA at room temperature shipped regular next day air; specimens obtained on Friday should be stored at 4°C and shipped Monday (no Saturday delivery)
  • Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
  • Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
  • Prenatal testing: Culture: A Confluent T25 flask of Amniocytes or chorionic villi. Maternal blood sample is required for maternal cell contamination studies. Direct specimens such as amniotic fluid or CVS cannot be tested.

A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.

Note: Counseling and informed consent are recommended for genetic testing. A consent form is available as a resource but not required.

INTERPRETATIVE DATA:

Prevalence: 1/10,000 to 1/30,000

Inheritance: Genomic imprinting; risk of recurrence depends in the genetic mechanism of loss of the paternally-contributed 15q11.2-q13 region (approximately 50% for imprint control defects; <1% for deletions or UPD).

Disease Characteristics: Severe hypotonia and feeding difficulties early, childhood-onset hyperphagia with resulting obesity, short stature, small hands and feet, hypogonadism, delayed motor milestones, delayed language development and cognitive impairment

Molecular Genetic Mechanism: The majority of patients (70%-75%) have interstitial deletions of the paternal chromosome 15q11.2-q13. Approximately 25%-29% have maternal disomy (UPD), 1% have chromosome 15 translocations and <1% have mutations of the imprint control region.

Related Tests: FISH, Prader-Willi syndrome

Method: Methylation-sensitive PCR using the 1st exon of the SNRPN gene

Analytical Sensitivity: Methylation analysis detects >99% of individuals with Prader-Willi syndrome

Test Limitations:
If test result is positive, further testing is required to identify the underlying molecular mechanism. Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms.

INDICATIONS FOR USE:

  • Patients suspected of having Prader-Willi syndrome based on clinical assessment

ADDITIONAL REFERENCES:

OMIM - www.omim.org/entry/176270
Genetics Home Reference - http://ghr.nlm.nih.gov/condition/prader-willi-syndrome
GeneReviews - www.ncbi.nlm.nih.gov/books/NBK1330/