The Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Med Genet A. 2013 Jan;161A(1):13-20. doi: 10.1002/ajmg.a.35651. Epub 2012 Dec 13.
Mosaicism for genome-wide paternal uniparental disomy (UPD) has been reported in only seven live born individuals to date. Clinical presentation includes manifestations of multiple paternal UPD syndromes with high variability, likely due to the variable levels of mosaicism in different somatic tissues. We report an eighth case in a female patient with mosaicism for genome-wide paternal UPD which highlights the complex clinical presentation. Our patient had features of Beckwith-Wiedemann syndrome (BWS), Angelman syndrome, and congenital hyperinsulinism. The clinical findings included prematurity, organomegaly, hemihyperplasia, developmental delay, benign tumors, and cystic lesions. The diagnosis in our patient was established utilizing microarray-based genome-wide DNA methylation analysis performed on leukocyte DNA. Targeted multiplex ligation-dependent probe amplification (MLPA) analysis of chromosome regions 11p15 and 15q13 confirmed mosaicism for paternal UPD at these genomic regions. This case represents the first report of microarray-based genome-wide DNA methylation analysis in the diagnosis of genome-wide paternal UPD. The application of microarray-based genome-wide DNA methylation analysis on selected individuals with complex clinical presentations could be a valuable diagnostic tool to improve the detection rate of mosaic genome-wide paternal UPD. This approach, which screens many loci simultaneously, is more cost-effective and less labor-intensive than performing multiple targeted DNA methylation-based assays. Identification of individuals with mosaicism for genome-wide paternal UPD is an important goal as it confers a low recurrence risk for the family and identifies individuals who require surveillance due to increased tumor risk.
迄今为止，仅在 7 名活产婴儿中报道了全基因组父源单亲二体性（UPD）嵌合体。临床表现包括多种父源 UPD 综合征的表现，具有高度可变性，这可能是由于不同体细胞组织中嵌合体的水平不同所致。我们报告了第 8 例女性全基因组父源 UPD 嵌合体病例，该病例突出了其复杂的临床表现。我们的患者具有 Beckwith-Wiedemann 综合征（BWS）、Angelman 综合征和先天性高胰岛素血症的特征。临床发现包括早产、器官肿大、偏侧肥大、发育迟缓、良性肿瘤和囊性病变。我们的患者通过对白细胞 DNA 进行基于微阵列的全基因组 DNA 甲基化分析来确诊。对 11p15 和 15q13 染色体区域进行靶向多重连接依赖性探针扩增（MLPA）分析，证实这些基因组区域存在父源 UPD 嵌合体。这是首例应用基于微阵列的全基因组 DNA 甲基化分析诊断全基因组父源 UPD 的病例。对具有复杂临床表现的选定个体进行基于微阵列的全基因组 DNA 甲基化分析可能是一种有价值的诊断工具，可提高全基因组父源 UPD 嵌合体的检出率。这种方法同时筛选多个位点，比进行多次基于靶向 DNA 甲基化的检测更具成本效益，且劳动强度更小。鉴定全基因组父源 UPD 嵌合体个体是一个重要目标，因为它可降低家族的复发风险，并确定由于肿瘤风险增加而需要进行监测的个体。
