Prader-Willi Syndrome SNRPN Methylation Analysis
Prader-Willi Syndrome (PWS) is a developmental disorder presenting at birth with hypotonia, low weight, weak cry, and poor sucking ability.
PrintPrader-Willi Syndrome (PWS) is a developmental disorder presenting at birth with hypotonia, low weight, weak cry, and poor sucking ability.
Other physical and developmental delays begin to present between 18-36 months, including severe obesity due to insatiable appetite, mild mental retardation, scoliosis, hypogonadism, hypopigmentation, as well as characteristic facies and behaviors.
Approximately 70-75% of PWS cases are attributed to an interstitial deletion of 15q11-q13 on the paternally inherited chromosome, with the remainder of Prader-Willi Syndrome cases caused by maternal uniparental disomy (24-28%) and imprinting center mutations (<1%).
The Ambry Test is Methylation Analysis of the SNRPN gene that allows discrimination between the maternal (methylated) and paternal (unmethylated) alleles. Prader-Willi Methylation can detect approximately 99% of described defects, including interstitial deletions, UPD, and imprinting center defects.
Angelman Syndrome is caused by disruption of maternal allele of UBE3A. For additional information about Angelman Syndrome testing please see the test entry for Angelman Syndrome.
Prader-Willi syndrome (PWS) is an autosomal dominant disease characterized by developmental and growth issues presenting from birth. The incidence of PWS varies from one in 10,000 to 25,0001 and affects both males and females worldwide. At birth, Prader-Willi patients usually have weak muscle tone, low birth weight, weak cry, and poor sucking ability. Other physical and developmental delays begin to present between 18-36 months, including severe obesity due to insatiable appetite, mild mental retardation, scoliosis, hypogonadism, hypopigmentation, as well as characteristic facies and behaviors.2 While there is no cure for PWS, effective disease management can include the administration of human growth hormone, behavior modifications, including balanced diet, food restrictions and exercise regiment, as well as physical and speech therapies.3
Prader-Willi syndrome is caused by the loss of paternally expressed genes within chromosome 15q11-q13.4 Approximately 70-75% of Prader-Willi cases are attributed to an interstitial deletion of 15q11-q13 on the paternally inherited chromosome, with the remainder of cases caused by maternal uniparental disomy (UPD, 24-28%) and imprinting center defects (<1%).1,3 Cases involving the 15q deletion have been associated with a higher frequency for special feeding techniques, elevated sleep disturbances, hypopigmentation, and speech defects.4 PWS cases involving maternal UPD are less likely to have the typical facial appearance, hypopigmentation, but more likely to have psychosis5 and autism spectrum disorders.
- Diagnostic testing for individuals known or suspected to have clinical features associated with Prader-Willi Syndrome for accurate risk assessment and for possible information on genotype/phenotype correlation. Early diagnosis is also beneficial for early intervention and treatment of PWS.
- Prenatal testing may be considered in families with a previous history of Prader-Willi syndrome.
For methylation testing, polymerase chain reaction (PCR) is used to selectively amplify regions of gDNA corresponding to exon 1 and its putative promoter of the SNRPN gene followed by sequencing on a pyrosequencing platform (Pyromark MD). Detecting the methylation pattern within the 15q11.2-13 locus allows for the discrimination between the maternal (methylated) and paternal (unmethylated) alleles. A total of 12 CpG dinucleotide sequences are analyzed for methylation status.
Methylation analysis is capable of detecting approximately 99% of described defects, including interstitial deletions, uniparental disomy (UPD), and imprinting center (IC) defects. The analytical detection rate is also approximately 99%.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 2400 | UBE3A Gene Sequence Analysis | 83891x1, 83894x11, 83898x10, 83904x23, 83909x23, 83912x1 |
| 2420 | Angelman Syndrome, X-Linked SLC9A6 | 83891x1, 83894x16, 83898x15, 83904x28, 83909x28, 83912x1 |
| 2440 | SNRPN Methylation | 83891x1, 83892x1, 83894x2, 83898x1, 83904x3, 83909x3, 83912x1 |
| 8520 | Angelman Syndrome SNRPN and UBE3A | 83891x1, 83892x1, 83894x12, 83898x11, 83904x26, 83909x26, 83912x2 |
| Technique | Days |
|---|---|
| UBE3A Gene Sequence Analysis | 14-21 |
| Angelman Syndrome, X-Linked SLC9A6 | 14-21 |
| SNRPN Methylation | 7-14 |
| Angelman Syndrome SNRPN and UBE3A |
1 Glenn C et al. Mol. Hum Repro. 1997; 3(4): 321-32.
2 Holm VA et al. Pediatrics 1993; 91(2): 398-402.
3 Scheimann A. (2006). Prader-Willi Syndrome. eMedicine, http://www.emedicine.com/ped/topic1880.htm. Accessed August 17, 2009.
4 Torrado M et al. Am J Med Genet A. 2007 Mar 1;143(5):460-8.
5 Holland AJ et al. Psychol Med. 2003; 33; 141-53.
6 Descheemaeker M.J et al. Am J Med Genet Part A.2006;140A: 1136-1142.