The clinical phenotype of mosaicism for genome-wide paternal uniparental disomy: Two new reports
The clinical phenotype of mosaicism for genome-wide paternal uniparental disomy: Two new reports
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DOI：
10.1002/ajmg.a.32172
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发表时间：
2008-01-15
影响因子：
2
通讯作者：
Algar, Elizabeth
中科院分区：
文献类型：
--
作者：
Wilson, Meredith;Peters, Gregory;Algar, Elizabeth
最近，嵌合体的全基因组父亲单亲二体（patUPD），归因于雄激素/双亲嵌合体，已被证明是胎盘间质发育不良（PMD），一个独特的囊性胎盘表型的基础。Beckwith-Wiedemann综合征（BWS）的表现在约三分之一的妊娠合并PMD的胎儿或活产婴儿中观察到。很少有报道描述活产个体在体细胞组织中具有经证实的全基因组patUPD嵌合现象。我们报告了另外两个具有复杂表型的儿童，包括BWS的一些发现，先天性高胰岛素血症性低血糖，长期喂养困难和婴儿期发育不良。第一个发展为身材矮小，双侧嗜铬细胞瘤和进行性动脉狭窄，第二个有先天性肾上腺囊肿，后来发展为肝母细胞瘤和斑片状色素沉着过度。KCNQ1OT1/LIT 1和H19基因座（11p15.5）的白细胞DNA甲基化研究显示，患者1几乎完全丧失了母体甲基化（LOM），患者2部分缺失了LOM。微卫星标记组显示整个11号染色体patUPD。在这两个SNP阵列研究与白细胞中的嵌合全基因组patUPD一致，而患者1的成纤维细胞DNA显示双亲遗传。本报告进一步阐明了嵌合体对全基因组patUPD的临床后果，导致复杂和可变的表型。应考虑在具有非典型UPD表型的个体中进行全基因组UPD研究。(c)2007 Wiley-Liss，Inc.
Recently, mosaicism for genome-wide paternal uniparental disomy (patUPD), attributed to androgenetic/biparental mosaicism, has been shown to underlie placental mesenchymal dysplasia (PMD), a distinctive cystic placental phenotype. Manifestations of Beckwith-Wiedemann syndrome (BWS) have been observed in approximately one-third of fetuses or livebom infants from pregnancies complicated by PMD. There are very few reports describing liveborn individuals with proven mosaicism for genome-wide patUPD in somatic tissues. We report two further children with complex phenotypes including some findings of BWS, congenital hyperinsulinemic hypoglycemia, prolonged feeding difficulty and failure to thrive in infancy. The first developed short stature, bilateral pheochromocytomas and progressive arterial stenoses, and the second had congenital adrenal cysts, and later developed hepatoblastoma and patchy hyperpigmentation. Leukocyte DNA methylation studies of KCNQ1OT1/LIT1 and H19 loci (11p15.5) showed almost complete loss of maternal methylation (LOM) in patient 1 and partial LOM in patient 2. Microsatellite marker panels showed whole chromosome 11 patUPD. SNP array studies in both were consistent with mosaic genome-wide patUPD in leukocytes, while fibroblast DNA in Patient 1 showed biparental inheritance. This report further illustrates the clinical consequences of mosaicism for genome-wide patUPD, which results in complex and variable phenotypes. Studies for genome-wide UPD should be considered in individuals with atypical UPD phenotypes. (c) 2007 Wiley-Liss, Inc.