title: Prenatal diagnosis of complete maternal uniparental isodisomy of chromosome 4 in a fetus without congenital abnormality or inherited disease-associated variations.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: WeiQiang
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: HuiMin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127 P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: GuoJiu
authors.initials: G
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: WenJun
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Prenatal Diagnosis and Fetal Medical, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150 P. R. China.
authors.forename: ZhiHua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Prenatal Diagnosis and Fetal Medical, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150 P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, P. R. China.
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.affiliation: 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.
authors.forename: XiaoFang
authors.initials: X
authors.lastname: Sun
keywords: Chromosomal microarray analysis; Chromosome 4; Ultrasound; Uniparental isodisomy; Whole exome sequencing