Table 1.

Summary of Testing Used in Prader-Willi Syndrome

Test MethodGenetic Mechanisms Detected 1Proportion of PWS Detected by Test Method
DNA methylation 2Deletions, UPD & ID>99%
MS-MLPA 3Deletions, UPD & ID>99%
FISH 4Deletions65%-75%
CMA 5Deletions65%-75%
CMA-SNP array 6Deletions & some UPDs80%-90%
DNA polymorphisms 7UPD and ID20%-30%
DNA sequence 8ID with IC deletions<1%

ID = imprinting defect

IC = imprinting center


See Molecular Genetics for more details.


Can establish diagnosis, but will not distinguish genetic mechanism; can be done by Southern blot or methylation-specific PCR.


Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA):
 • Will distinguish deletion from disomy (UPD and ID);
 • Detects five parent-specific methylation sites;
 • Will not distinguish UPD from ID;
 • Can give approximate size of deletion and identify type 1 and 2 deletions (see Figure 2);
 • Can also detect most IC and SNORD116 microdeletions (see Figure 2; Molecular Genetic Pathogenesis).


FISH is typically done in conjunction with a karyotype. Information is limited to AS/PWS region and the specific probes used (e.g., SNRPN). FISH does not query the whole AS/PWS region and will miss small deletions. It does not give information about the rest of the chromosomes, and does not distinguishbetween normal, UPD, and ID.


Chromosomal microarray (CMA) has a slightly higher detection frequency than FISH and will provide detailed information regarding size of the deletion. Also, it gives information regarding deletions and duplication in the remainder of the genome. CMA is far more precise than karyotype and FISH; it will detect SNORD116 microdeletions (see Figure 2 and Molecular Genetic Pathogenesis).


Same as CMA; in addition, use of small nucleotide polymorphisms (SNP) will allow detection of UPD in cases with long stretches of homozygosity.


Not a first line test; performed after DNA methylation analysis diagnoses PWS, but FISH or CMA analysis indicates disomy.


DNA sequencing has a very specific role in IDs to distinguish IC deletions from epimutations. It is limited to a region of <4.3 kb in the PWS IC smallest region of deletion overlap (SRO) [Ohta et al 1999]. The map location is approximately 25,196,494 to 25,200,794 bp [UCSC Genome Browser, hg19].

From: Prader-Willi Syndrome

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