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
2012 AMA code: 81331
TESTING METHODOLOGY: Methylation analysis
  • 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.

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