title: Prenatal diagnosis of chromosomal abnormalities in fetuses with abnormal cardiac ultrasound findings: evaluation of chromosomal microarray-based analysis.
abstract: OBJECTIVE
  To assess the frequency of karyotype abnormalities and chromosome 22q11.2 deletion syndrome among fetuses with abnormal cardiac ultrasound findings, and to evaluate the clinical value of chromosomal microarray-based analysis (CMA) in the study of such pregnancies.
  
  
  METHODS
  First, we carried out retrospective analysis of karyotype abnormalities and 22q11.2 deletion syndrome cases diagnosed between January 2009 and December 2011 in our center among fetuses with abnormal cardiac ultrasound findings (n = 276). Second, CMA was performed in 51 of the fetuses with such findings, normal karyotype and negative or no 22q11.2 deletion syndrome study, and in the only fetus with a heart defect and an apparently balanced de novo chromosomal rearrangement.
  
  
  RESULTS
  Out of the 276 pregnancies with abnormal cardiac ultrasound findings, karyotyping revealed a chromosomal abnormality in 44 (15.9%). Of fetuses with normal karyotype in which 22q11.2 deletion syndrome studies were performed, 6.4% (5/78) had this microdeletion syndrome. Among fetuses with abnormal cardiac findings, normal karyotype and negative or no 22q11.2 deletion syndrome study that underwent CMA, the detection rate of pathogenic copy number variants not detected by conventional cytogenetics was 2.0% (1/51), and no variants of uncertain clinical significance were found. In the fetus with a heart defect and an apparently balanced de novo chromosomal rearrangement, CMA revealed that the rearrangement was not truly balanced.
  
  
  CONCLUSIONS
  In the assessment of genetic abnormalities in pregnancies with abnormal cardiac ultrasound findings, the diagnostic yield may be increased by 2% if CMA is used as a complementary tool to conventional cytogenetics. Our results suggest that CMA could be a good alternative to karyotyping in these pregnancies.
authors.affiliation: Servei de Bioquímica i Genètica Molecular, Hospital Clínic, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Mademont-Soler
authors.forename: C
authors.initials: C
authors.lastname: Morales
authors.forename: A
authors.initials: A
authors.lastname: Soler
authors.forename: J M
authors.initials: JM
authors.lastname: Martínez-Crespo
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: E
authors.initials: E
authors.lastname: Margarit
authors.forename: N
authors.initials: N
authors.lastname: Clusellas
authors.forename: M
authors.initials: M
authors.lastname: Obón
authors.forename: B L
authors.initials: BL
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Sánchez
mesh_terms: D059786:Abnormal Karyotype; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics; D004452:Echocardiography; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007621:Karyotyping; D046228:Microarray Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies