Prader-Willi syndrome (PWS) is caused by the loss of function of the paternally inherited 15q11-q13 locus. This region is governed by genomic imprinting, a phenomenon in which genes are expressed exclusively from one parental allele. The genomic imprinting of the 15q11-q13 locus is established in the germline and is largely controlled by a bipartite imprinting centre. One part, termed the Prader-Willi syndrome imprinting center (PWS-IC), comprises a CpG island that is unmethylated on the paternal allele and methylated on the maternal allele. The second part, termed the Angelman syndrome imprinting centre, is required to silence the PWS_IC in the maternal germline. The loss of the paternal contribution of the imprinted 15q11-q13 locus most frequently occurs owing to a large deletion of the entire imprinted region but can also occur through maternal uniparental disomy or an imprinting defect. While PWS is considered a contiguous gene syndrome based on large-deletion and uniparental disomy patients, the lack of expression of only non-coding RNA transcripts from the SNURF-SNRPN/SNHG14 may be the primary cause of PWS. Patients with small atypical deletions of the paternal SNORD116 cluster alone appear to have most of the PWS related clinical phenotypes. The loss of the maternal contribution of the 15q11-q13 locus causes a separate and distinct condition called Angelman syndrome. Importantly, while much has been learned about the regulation and expression of genes and transcripts deriving from the 15q11-q13 locus, there remains much to be learned about how these genes and transcripts contribute at the molecular level to the clinical traits and developmental aspects of PWS that have been observed.

Prader-Willi 综合征 (PWS) 是由父系遗传的 15q11-q13 基因座功能丧失引起的。该区域受基因组印记控制，这是一种基因仅由一个亲本等位基因表达的现象。 15q11-q13 基因座的基因组印记是在种系中建立的，并且主要由二分印记中心控制。其中一部分被称为普瑞德-威利综合征印记中心 (PWS-IC)，由一个 CpG 岛组成，该岛在父亲等位基因上未甲基化，在母亲等位基因上甲基化。第二部分被称为天使综合征印记中心，需要沉默母体种系中的 PWS_IC。印记 15q11-q13 位点父系贡献的丧失最常因整个印记区域的大量缺失而发生，但也可能因母本单亲二体性或印记缺陷而发生。虽然 PWS 被认为是一种基于大缺失和单亲二倍体患者的连续基因综合征，但SNURF-SNRPN/SNHG14中仅非编码 RNA 转录物的表达缺乏可能是 PWS 的主要原因。仅具有父系SNORD116簇小非典型缺失的患者似乎具有大多数 PWS 相关的临床表型。 15q11-q13 基因座母体贡献的丧失会导致一种单独且独特的疾病，称为天使综合征。重要的是，虽然我们对源自 15q11-q13 位点的基因和转录本的调控和表达有了很多了解，但关于这些基因和转录本如何在分子水平上对 PWS 的临床特征和发育方面做出贡献，还有很多有待了解。已观察到的。