Institute of Human Genetics, University of Bonn, Bonn, Germany.
Children's Hospital, University of Bonn, Bonn, Germany.
Am J Med Genet A. 2019 Nov;179(11):2252-2256. doi: 10.1002/ajmg.a.61314. Epub 2019 Aug 1.
A male patient with mosaic paternal uniparental diploidy (PUD) is presented. After birth, the patient presented with hypoglycemia, hemihypertrophy, umbilical hernia, and hepatomegaly. Afterward pancreatic hypertrophy, liver hemangiomas, and cysts were detected sonographically. At the age of 3.5 months, hepatoblastoma was diagnosed. To investigate suspected Beckwith-Wiedemann syndrome (BWS), extensive genetic analyses were performed using DNA from chorionic villus sampling, amniocentesis, and peripheral blood lymphocytes (chromosome analysis, methylation-specific multiplex ligation-dependent probe amplification assays, microsatellite analyses, and single nucleotide polymorphism array analysis). These analyses led to the detection of mosaic PUD. In peripheral blood lymphocytes, a male cell line (46,XY[27]/46,XX[5]) predominated, suggesting a mixture of uniparental isodisomy and heterodisomy. The genetic analyses suggest that the mosaic PUD status was attributable to fertilization of an oocyte by two sperms, with subsequent triploidy rescue giving rise to haploidy, which in turn was rescued. Notably, in the majority of the 28 mosaic PUD patients reported to date, BWS was initially suspected. Mosaic PUD status is associated with a higher risk for a broad range of malignant and benign tumors than in BWS. As tumors can also occur after childhood surveillance into adolescence is indicated. Mosaic PUD must therefore be considered in patients with suspected BWS.
一位患有镶嵌性父源单亲二倍体(PUD)的男性患者被呈现。出生后,该患者表现为低血糖、偏侧肥大、脐疝和肝肿大。此后,超声检查发现胰腺肥大、肝血管瘤和囊肿。在 3.5 个月大时,被诊断为肝母细胞瘤。为了调查疑似贝克威思-威德曼综合征(BWS),使用绒毛膜绒毛取样、羊膜穿刺术和外周血淋巴细胞(染色体分析、甲基化特异性多重连接依赖性探针扩增检测、微卫星分析和单核苷酸多态性微阵列分析)中的 DNA 进行了广泛的遗传分析。这些分析导致了镶嵌性 PUD 的检测。在外周血淋巴细胞中,一个男性细胞系(46,XY[27]/46,XX[5])占主导地位,提示存在单亲同二倍体和异二倍体的混合。遗传分析表明,镶嵌性 PUD 状态归因于一个卵子被两个精子受精,随后三倍体挽救产生单倍体,单倍体又被挽救。值得注意的是,在迄今为止报道的 28 例镶嵌性 PUD 患者中,大多数最初被怀疑为 BWS。与 BWS 相比,镶嵌性 PUD 状态与广泛的恶性和良性肿瘤风险增加相关。由于肿瘤也可能在儿童监测进入青春期后发生,因此需要进行青春期后监测。因此,在疑似 BWS 的患者中必须考虑到镶嵌性 PUD。