title: Karyotypic and molecular genetic changes associated with fetal cardiovascular abnormalities: results of a retrospective 4-year ultrasonic diagnosis study.
abstract: OBJECTIVE
  To investigate the incidence of aneuploidy in fetuses with congenital heart defects (CHDs) and to further identify submicroscopic changes and global DNA methylation levels as potential biomarkers in complex CHD cases.
  
  
  METHODS
  Fetuses at high risk for birth defects or with obvious sonographic anomalies were recruited at the Prenatal Diagnosis Center and Ultrasonic Diagnosis Center. Elective fetal karyotyping and DNA copy number and promoter methylation analyses were carried out following parental consent. G-banded karyotyping was performed to detect fetal aneuploidy. Copy number variations (CNVs) were detected using the Affymetrix SNP Array 6.0 and validated by real time PCR. Global DNA methylation analyses were conducted using a Roche NimbleGen Human DNA Methylation 3x720K Array, and DNA methylation differences were assayed by a Sequenom MassARRAY EpiTYPER.
  
  
  RESULTS
  Conventional karyotyping identified 30 cases with aneuploidy in 179 CHD fetuses. Various CNVs were found in two aneuploid fetuses and in five euploid CHD fetuses. Verified segmental deletion or duplications were not directly associated with cardiovascular malformations except in DAAM1 and GATA6. Verifiable aberrant DNA methylation could not be identified in three complex CHD fetuses.
  
  
  CONCLUSIONS
  In this study, Trisomy 18, Trisomy 21 and 45,XO were the most common aneuploidies identified in CHD fetuses. In the affected samples, only DAAM1 deletion and GATA6 amplification could be associated with cardiovascular biological processes.
authors.affiliation: Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Bihui
authors.initials: B
authors.lastname: Bao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Li
authors.forename: Shuai
authors.initials: S
authors.lastname: Tang
authors.forename: Lihong
authors.initials: L
authors.lastname: Zheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000782:Aneuploidy; D015415:Biomarkers / Q000378:metabolism*; D018376:Cardiovascular Abnormalities / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D056915:DNA Copy Number Variations / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005333:Fetus / Q000473:pathology*; D006801:Humans; D007621:Karyotyping; D012189:Retrospective Studies; D016216:Ultrasonography, Prenatal / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: Congenital heart defect; Copy number variants; Karyotyping; Methylation level.