Bieth Eric, Eddiry Sanaa, Gaston Véronique, Lorenzini Françoise, Buffet Alexandre, Conte Auriol Françoise, Molinas Catherine, Cailley Dorothée, Rooryck Caroline, Arveiler Benoit, Cavaillé Jérome, Salles Jean Pierre, Tauber Maïthé
Service de Génétique Médicale, CHU Toulouse-Purpan, Hôpital Purpan, Place du Docteur Baylac, Toulouse, France.
Centre de Physiopathologie de Toulouse-Purpan, INSERM UMR 1043; CNRS UMR 5282, Université Paul Sabatier, Toulouse, France.
Eur J Hum Genet. 2015 Feb;23(2):252-5. doi: 10.1038/ejhg.2014.103. Epub 2014 Jun 11.
The SNORD116 locus lies in the 15q11-13 region of paternally expressed genes implicated in Prader-Willi Syndrome (PWS), a complex disease accompanied by obesity and severe neurobehavioural disturbances. Cases of PWS patients with a deletion encompassing the SNORD116 gene cluster, but preserving the expression of flanking genes, have been described. We report a 23-year-old woman who presented clinical criteria of PWS, including the behavioural and nutritional features, obesity, developmental delay and endocrine dysfunctions with hyperghrelinemia. We found a paternally transmitted highly restricted deletion of the SNORD116 gene cluster, the shortest described to date (118 kb). This deletion was also present in the father. This finding in a human case strongly supports the current hypothesis that lack of the paternal SNORD116 gene cluster has a determinant role in the pathogenesis of PWS. Moreover, targeted analysis of the SNORD116 gene cluster, complementary to SNRPN methylation analysis, should be carried out in subjects with a phenotype suggestive of PWS.
SNORD116基因座位于父系表达基因的15q11 - 13区域，这些基因与普拉德 - 威利综合征（PWS）有关，PWS是一种伴有肥胖和严重神经行为障碍的复杂疾病。已有报道PWS患者存在包含SNORD116基因簇的缺失，但侧翼基因的表达得以保留。我们报告了一名23岁女性，她呈现出PWS的临床标准，包括行为和营养特征、肥胖、发育迟缓以及伴有高胃泌素血症的内分泌功能障碍。我们发现了父系遗传的SNORD116基因簇高度局限的缺失，这是迄今为止所描述的最短缺失（118 kb）。父亲也存在这种缺失。在人类病例中的这一发现有力地支持了当前的假说，即父系SNORD116基因簇的缺失在PWS发病机制中起决定性作用。此外，对于具有PWS疑似表型的受试者，应进行SNORD116基因簇的靶向分析，作为与SNRPN甲基化分析互补的检测手段。
