Prader-Willi Syndrome, Methylation Analysis

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PRADER-WILLI SYNDROME, METHYLATION ANALYSIS

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: Confluent T25 Amniocyte flasks. Maternal blood sample is required for maternal cell contamination studies.

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.
 
 
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: