Liu WeiQiang, Zhang HuiMin, Wang Jian, Yu GuoJiu, Qiu WenJun, Li ZhiHua, Chen Min, Choy Kwong Wai, Sun XiaoFang
Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150 P. R. China.
Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127 P. R. China.
Mol Cytogenet. 2015 Nov 4;8:85. doi: 10.1186/s13039-015-0190-z. eCollection 2015.
The prenatal diagnosis of subjects with complete uniparental isodisomy of chromosome 4 (iUPD4) has rarely been reported and poses a great challenge for genetic counseling. In this study, a prenatal case with a high (1 in 58) risk of Down syndrome was diagnosed with iUPD4 by combined chromosomal microarray analysis (CMA), whole exome sequencing (WES) and ultrasound morphology scan.
By CMA, a pathogenic copy number variant was not detected; however, a complete maternal iUPD4 was identified in this fetus after analyzing the parental genotype results. To detect potentially autosomal recessive variants, WES was performed. Two missense and two frameshift variants were identified but were predicted with uncertain significance; none of the mutations were definitively associated with congenital abnormality or inherited disease. In addition, a detailed ultrasound morphology scan did not identify any structural abnormalities, facial dysmorphisms or intrauterine growth restriction. The family history was unremarkable. The couple was counseled with the prenatal diagnostic results, and they opted to give birth to the child. No phenotypic abnormalities were observed in this child after the first year of life.
This study provides further evidence that iUPD4 can result in a healthy live birth and demonstrates that the combined use of CMA, WES and ultrasound technology provides additional information for the prenatal diagnosis and clinical management of rare UPD events.
4号染色体单亲二体完全性（iUPD4）患者的产前诊断鲜有报道，对遗传咨询构成了巨大挑战。在本研究中，通过染色体微阵列分析（CMA）、全外显子组测序（WES）和超声形态学扫描，诊断出一例唐氏综合征风险较高（1/58）的产前病例为iUPD4。
通过CMA未检测到致病性拷贝数变异；然而，在分析父母基因型结果后，在该胎儿中鉴定出完全性母源iUPD4。为了检测潜在的常染色体隐性变异，进行了WES。鉴定出两个错义变异和两个移码变异，但预测其意义不明确；没有一个突变与先天性异常或遗传性疾病明确相关。此外，详细的超声形态学扫描未发现任何结构异常、面部畸形或宫内生长受限。家族史无异常。向这对夫妇提供了产前诊断结果的咨询，他们选择生下这个孩子。该儿童在出生后第一年未观察到表型异常。
本研究进一步证明iUPD4可导致健康活产，并表明CMA、WES和超声技术的联合应用为罕见单亲二体事件的产前诊断和临床管理提供了额外信息。
