title: Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature.
abstract: OBJECTIVE
  To evaluate the results of prenatal chromosomal microarray analysis (CMA) on >1000 fetal samples referred for testing at our institution and to compare these data to published reports.
  
  
  METHODS
  High resolution CMA was offered to women undergoing amniocentesis or chorionic villus sampling. Parental samples were obtained concurrently to exclude maternal cell contamination and assist interpretation of copy number variations.
  
  
  RESULTS
  Clinically significant copy number variations were observed in 85/1115 cases (7.6%) overall, and in 45/1075 cases (4.2 %) if 40 abnormal cases with known chromosome abnormalities or familial genomic imbalances were excluded. Eighteen of the 1115 cases had variants of unclear clinical significance (1.6%). Indications yielding the most clinically significant findings were abnormal karyotype/fluorescence in situ hybridization (26/61, 42.6%), family history of chromosomal abnormality (13/137, 9.5%), abnormal ultrasound (38/410, 9.3%), abnormal serum screening (2/37, 5.4%) and advanced maternal age (5/394, 1.3%). Of 1075 cases having no previously known cytogenetic abnormality or family history, 18 (1.7%) had clinically significant genomic changes undetectable by conventional prenatal chromosome analysis.
  
  
  CONCLUSIONS
  Current experience confirms that the detection rate of CMA for prenatal chromosomal abnormalities surpasses that of conventional karyotype analysis and continues to improve with higher resolution arrays, while maintaining a low frequency of results of unclear clinical significance.
authors.affiliation: Medical Genetics Laboratories, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Breman
authors.forename: Amber N
authors.initials: AN
authors.lastname: Pursley
authors.forename: Patricia
authors.initials: P
authors.lastname: Hixson
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
authors.forename: Patricia
authors.initials: P
authors.lastname: Ward
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Chad
authors.initials: C
authors.lastname: Shaw
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Arthur
authors.initials: A
authors.lastname: Beaudet
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Sau W
authors.initials: SW
authors.lastname: Cheung
authors.forename: Ignatia
authors.initials: I
authors.lastname: Van den Veyver
mesh_terms: D059786:Abnormal Karyotype; D000328:Adult; D000649:Amniocentesis / Q000379:methods*; D000653:Amniotic Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D015193:Chorionic Villi Sampling / Q000379:methods*; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D004247:DNA / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011247:Pregnancy; D013781:Texas / Q000453:epidemiology; D016216:Ultrasonography, Prenatal
chemical_list: D004247:DNA