title: Copy Number Variations with Isolated Fetal Ventriculomegaly.
abstract: BACKGROUND
  Copy Number Variations (CNVs) are an important genetic cause of a number of neurodevelopmental disorders (NDs). However, the association between CNVs and the development and prognosis of fetal isolated mild ventriculomegaly (IMV) is unclear.
  
  
  OBJECTIVE
  To investigate possible associations between CNVs and the development of fetal IMV.
  
  
  METHODS
  This retrospective study recruited 154 subjects with ultrasound-confirmed fetal IMV and 190 subjects in a control cohort who underwent a high-risk prenatal serum screening program. The exclusion criteria included fetus G-banding chromosomal abnormality or positive fetus TORCH infection. DNA samples from all 344 fetuses were examined by an SNP-array. Developmental outcomes were assessed during postnatal follow-up.
  
  
  RESULTS
  Fourteen pathogenic CNVs (pCNVs) were identified in 13 out of 154 IMV fetuses. Three pCNVs were found in 3 out of 190 subjects in the prenatal screening high-risk cohort, with a significant difference (P value=0.016, X2 test). Notably, the 14 pCNVs detected in the IMV cohort were all associated with neurodevelopmental disorders (NDs), including autism, intellectual disability. Among the 13 IMV fetuses carrying pCNVs, five subjects were found in the postnatal follow-up to manifest NDs, including two with autism and three with mild neurodevelopmental delay. The other 8 subjects consisted of three normal infants younger than 12-months old, two lost in the follow-up, and three with the termination of pregnancy. Out of 141 IMV subjects without detectable pCNVs, 123 subjects showed normal development, 16 were lost in the follow-up, 2 subjects terminated the pregnancy due to fetal hydrocephalus or congenital heart disease in the late fetus development.
  
  
  CONCLUSIONS
  This study suggests an association between pCNVs and fetal IMV. pCNVs may be involved in the pathological process of fetal IMV and postnatal NDs. Identifying specific genomic alterations may provide an insight into pathogenetic mechanism and aid better diagnosis and prognosis of neurodevelopmental outcomes in fetal IMV.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210029. China.
authors.forename: P
authors.initials: P
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210029. China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing. China.
authors.forename: R
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Ultrasound, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210029. China.
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, 20 Renminnan Road, Chengdu, Sichuan 610041. China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210029. China.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210029. China.
authors.forename: C
authors.initials: C
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210029. China.
authors.forename: D
authors.initials: D
authors.lastname: Ma
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093. United States.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093. United States.
authors.forename: X
authors.initials: X
authors.lastname: Fu
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093. United States.
authors.forename: W
authors.initials: W
authors.lastname: Shi
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Institute, University of California San Diego, La Jolla, CA 92093. United States.
authors.forename: S
authors.initials: S
authors.lastname: Yi
authors.affiliation: Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093. United States.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan. China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing. China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
mesh_terms: D006332:Cardiomegaly / Q000151:congenital* / Q000175:diagnosis*; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000235:genetics*; D006352:Heart Ventricles / Q000002:abnormalities*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D063868:Patient Outcome Assessment; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome; D016216:Ultrasonography, Prenatal
keywords: Fetal ventriculomegaly; autism; copy number variant; mental retardation; prenatal diagnosis