title: [Application of whole-genome and high-resolution chromosome microarray analysis for the investigation of fetuses with ultrasound abnormalities].
abstract: OBJECTIVE
  To assess the value of whole-genome high-resolution chromosome microarray analysis (CMA) for the investigation of fetuses with ultrasound abnormalities.
  
  
  METHODS
  Whole genome high-resolution CytoScanHD array from Affymetrix was employed to investigate 651 fetuses with structural abnormalities detected by ultrasound, for whom standard G-banded chromosome analysis has revealed a normal karyotype. The fetuses were divided into a single malformation group (n=264) and a multiple malformations group (n=387). In total there were 130 chorionic villus samples, 192 amniotic fluid samples and 329 cord blood samples. Extraction of fetal DNA and CMA experiment have followed the standard guidelines from the manufacturers. All copy number variations (CNVs) detected by CMA were confirmed by fluorescence in situ hybridization (FISH) or real-time polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  CMA analysis has detected genomic CNVs in 475 (73%) cases. Clinically significant CNVs were found in 11.5% (75/651) of fetuses, including two uniparental disomies (UPD) and two cryptic mosaicisms. Variations of unknown significance (VOUS) was found in 2.0% (13/651) of tested fetuses.
  
  
  CONCLUSIONS
  Above results have suggested that whole-genome and high-resolution CMA is valuable for the analysis of fetuses with structural abnormalities detected by ultrasound, which can increase the detection rate by approximately 11%. CMA using single nucleotide polymorphism (SNP) array has the ability to detect UPD and low-level mosaicisms. Sufficient communication between technicians and genetic counselors, parental testing and comparison the results with in-house and relevant online databases can significantly reduce the rate of VOUS.
authors: Prenatal Diagnostic Center, Guangzhou Women and Chilren's Medical Centre, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China. canliao@hotmail.com.
authors: Yan
authors: Y
authors: Zhang
authors: Fang
authors: F
authors: Fu
authors: Ru
authors: R
authors: Li
authors: Guie
authors: G
authors: Xie
authors: Jin
authors: J
authors: Han
authors: Min
authors: M
authors: Pan
authors: Li
authors: L
authors: Zhen
authors: Xin
authors: X
authors: Yang
authors: Dongzhi
authors: D
authors: Li
authors: Can
authors: C
authors: Liao
mesh_terms: D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D007621:Karyotyping; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D014463:Ultrasonography