Anderlid Britt-Marie, Lundin Johanna, Malmgren Helena, Lehtihet Mikael, Nordgren Ann
Department of Molecular Medicine and Surgery, Clinal Genetic Unit, Centre of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Am J Med Genet A. 2014 Feb;164A(2):425-31. doi: 10.1002/ajmg.a.36307. Epub 2013 Dec 5.
Genetic analyses were performed in a male patient with suspected Prader-Willi syndrome who presented with hypogonadism, excessive eating, central obesity, small hands and feet and cognition within the low normal range. However, he had no neonatal hypotonia or feeding problems during infancy. Chromosome analysis showed a normal male karyotype. Further analysis with array-CGH identified a mosaic 847 kb deletion in 15q11-q13, including SNURF-SNRPN, the snoRNA gene clusters SNORD116 (HBII-85), SNORD115, (HBII-52), SNORD109 A and B (HBII-438A and B), SNORD64 (HBII-13), and NPAP1 (C15ORF2). MLPA confirmed the deletion and the results were compatible with a paternal origin. Metaphase-FISH verified the mosaicism with the deletion present in 58% of leukocytes analyzed. Three smaller deletions in this region have previously been reported in patients with Prader-Willi syndrome phenotype. All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome. Furthermore, it examplifies diagnostic difficulties in atypical cases and illustrates the need for additional testing methods when Prader-Willi syndrome is suspected.
对一名疑似普拉德-威利综合征的男性患者进行了基因分析，该患者表现为性腺功能减退、暴饮暴食、中心性肥胖、手足较小且认知处于低正常范围。然而，他在婴儿期没有新生儿肌张力减退或喂养问题。染色体分析显示为正常男性核型。采用阵列比较基因组杂交（array-CGH）进一步分析发现15q11-q13存在一个847 kb的嵌合缺失，包括SNURF-SNRPN、小核仁RNA基因簇SNORD116（HBII-85）、SNORD115（HBII-52）、SNORD109 A和B（HBII-438A和B）、SNORD64（HBII-13）以及NPAP1（C15ORF2）。多重连接探针扩增（MLPA）证实了该缺失，结果与父源起源相符。中期荧光原位杂交（Metaphase-FISH）验证了嵌合现象，在所分析的58%白细胞中存在该缺失。此前在具有普拉德-威利综合征表型的患者中已报道过该区域的三个较小缺失。所有这三个缺失都包括SNORD116，但只有两个包含SNURF-SNRPN的部分，提示SNORD116是普拉德-威利表型的主要促成因素。我们的病例增加了关于基因型-表型相关性的更多信息，并支持SNORD116在普拉德-威利综合征发病机制中起主要作用的假说。此外，它例证了非典型病例的诊断困难，并说明了在怀疑普拉德-威利综合征时需要额外的检测方法。
