Chen Qi, Chen Yunpeng, Shi Lin, Tao Ying, Li Xiaoguang, Zhu Xiaolan, Yang Yan, Xu Wenlin
Genetic and Prenatal Diagnosis Center, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Department of Ultrasound, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Front Genet. 2023 Oct 4;14:1232059. doi: 10.3389/fgene.2023.1232059. eCollection 2023.
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.
单亲二体（UPD）是指两条同源染色体均仅从一个亲本遗传而来，而未从另一个亲本遗传到相同拷贝。关于UPD临床表型的研究通常集中在已记录的UPD 6、7、11、14、15和20上，这些会直接导致印记障碍。本研究分别描述了3例UPD 2、9和14患者的临床表型和基因发现。进行了染色体微阵列（CMA）、UPDtool、甲基化特异性多重连接依赖探针扩增（MS-MLPA）和全外显子测序（WES）分析以确定遗传病因。CMA显示2号和9号染色体全为纯合区域，14号染色体部分为纯合区域。UPD-tool显示UPD2来自父系。MS-MLPA显示在UPD14病例中，母源印记基因MEG3发生低甲基化。此外，UPD14病例表现出复杂症状，包括生长发育迟缓、肌张力低下和急性呼吸窘迫综合征（ARDS），WES分析显示伴有多个杂合基因型的基因突变。此外，我们回顾了已记录的UPD病例并总结了临床特征和预后。本研究强调了通过基因检测确认UPD诊断和来源的重要性。因此，建议扩展详细的表型和基因型可为分子检测和遗传咨询提供有效指导，并促进对印记障碍及伴随的拷贝数变异潜在机制的进一步生物学研究。
