PDF(Pubmed)
Abstract：
Uniparental disomy (UPD) refers to as both homologous chromosomes inherited from only one parent without identical copies from the other parent. Studies on clinical phenotypes in UPDs are usually focused on the documented UPD 6, 7, 11, 14, 15, and 20, which directly lead to imprinting disorders. This study describes clinical phenotypes and genetic findings of three patients with UPD 2, 9, and 14, respectively. Chromosomal microarray (CMA), UPDtool, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and whole-exome sequencing (WES) analysis were performed to characterize the genetic etiology. The CMA revealed a homozygous region involving the whole chromosome 2 and 9, a partial region of homozygosity in chromosome 14. UPD-tool revealed a paternal origin of the UPD2. MS-MLPA showed hypomethylation of imprinting gene MEG3 from maternal origin in the UPD14 case. In addition, UPD14 case displayed complex symptoms including growth failure, hypotonia and acute respiratory distress syndrome (ARDS), accompanied by several gene mutations with heterozygous genotype by WES analysis. Furthermore, we reviewed the documented UPDs and summarized the clinical characteristics and prognosis. This study highlighted the importance to confirm the diagnosis and origin of UPD using genetic testing. Therefore, it is suggested that expanding of the detailed phenotypes and genotypes provide effective guidance for molecule testing and genetic counseling, and promote further biological investigation to the underlying mechanisms of imprinted disorders and accompanied copy number variations.
摘要：
单亲二体(UPD)是指两个同源染色体仅从一个亲本遗传而没有来自另一个亲本的相同拷贝。对UPDs中临床表型的研究通常集中在记录的UPD6、7、11、14、15和20上，这些直接导致印记障碍。这项研究描述了3例UPD2、9和14患者的临床表型和遗传发现。染色体微阵列(CMA),UPDtool,甲基化特异性多重连接依赖性探针扩增（MS-MLPA）和全外显子组测序（WES）分析以表征遗传病因。CMA揭示了涉及整个2号和9号染色体的纯合区域，这是14号染色体纯合性的部分区域。UPD工具揭示了UPD2的父系起源。在UPD14病例中，MS-MLPA显示来自母体来源的印迹基因MEG3的低甲基化。此外,UPD14病例表现出复杂的症状，包括生长障碍，张力减退和急性呼吸窘迫综合征（ARDS），通过WES分析，伴有几种具有杂合基因型的基因突变。此外，我们回顾了记录的UPDs,并总结了其临床特征和预后.这项研究强调了使用基因检测确认UPD的诊断和起源的重要性。因此,建议详细的表型和基因型的扩展为分子检测和遗传咨询提供有效的指导，并促进对印迹障碍和伴随拷贝数变异的潜在机制的进一步生物学研究。
