Defects in 15q11.2-q13 consistent with PWS | Percent of PWS cases | Molecular findings | Risk of recurrence in future siblings (percent) | Parental follow-up testing |
Deletions of PWS-critical region on paternal 15q11-q13 | 65 to 75 |
| <1¶ | Consider paternal karyotype to look for chromosomal rearrangement |
Maternal uniparental disomy | 20 to 30Δ |
| <1¶ | Karyotype of the proband to rule out Robertsonian translocation (rare) |
Imprinting center defects | ||||
Epimutations without deletion | 2 |
| <1 | |
Deletion | <0.5 |
| Up to 50 | Paternal sequencing (SNRPN gene) for deletion |
PWS: Prader-Willi syndrome; FISH: fluorescence in situ hybridization; CMA: chromosomal microarray; DNA: deoxyribonucleic acid; SNP: single-nucleotide polymorphism.
* FISH also may be used for deletion analysis, but the analysis is less detailed than CMA.
¶ Rare defects with a substantial risk of recurrence in a sibling are chromosomal rearrangement (<1% of PWS cases) and maternal uniparental disomy with predisposing parental translocation or marker chromosome (<1% of PWS cases).
Δ The risk of maternal uniparental disomy probably rises with maternal age[2,3].
◊ Rarely, balanced or unbalanced chromosomal translocations involving chromosome 15 may result in PWS. Methylation is consistent with the presence of only the maternal allele in these cases[2].
§ Uniparental disomy analysis is ideally performed with parental karyotype but can also be done with microsatellite probes or SNPs of parents and child.Adapted from: Driscoll DJ, Miller JL, Schwartz S, and Cassidy SB. Prader-Willi Syndrome (1998 Oct 6 [Updated 2017 Dec 14]). In: Adam MP, Everman DB, Mirzaa GM, et al, editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1330/ (Accessed on September 14, 2022).
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