title: Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound.
abstract: OBJECTIVE
  The aim of this study is to understand the diagnostic utility of comparative genomic hybridization (CGH)-based microarrays for pregnancies with abnormal ultrasound findings.
  
  
  METHODS
  We performed a retrospective analysis of 2858 pregnancies with abnormal ultrasounds and normal karyotypes (when performed) tested in our laboratory using CGH microarrays targeted to known chromosomal syndromes with later versions providing backbone coverage of the entire genome. Abnormalities were stratified according to organ system involvement. Detection rates for clinically significant findings among these categories were calculated.
  
  
  RESULTS
  Clinically significant genomic alterations were identified in cases with a single ultrasound anomaly (n = 99/1773, 5.6%), anomalies in two or more organ systems (n = 77/808, 9.5%), isolated growth abnormalities (n = 2/76, 2.6%), and soft markers (n = 2/77, 2.6%). The following anomalies in isolation or with additional anomalies had particularly high detection rates: holoprosencephaly (n = 9/85, 10.6%), posterior fossa defects (n = 21/144, 14.6%), skeletal anomalies (n = 15/140, 10.7%), ventricular septal defect (n = 14/132, 10.6%), hypoplastic left heart (n = 11/68, 16.2%), and cleft lip/palate (n = 14/136, 10.3%).
  
  
  CONCLUSIONS
  Microarray analysis identified clinically significant genomic alterations in 6.5% of cases with one or more abnormal ultrasound findings; the majority were below the resolution of karyotyping. Larger data sets such as this allow for sub-stratification by specific anomalies to determine risks for genomic alterations detectable by microarray analysis.
authors: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington, USA. lisa.shaffer@perkinelmer.com
authors: Lisa G
authors: LG
authors: Shaffer
authors: Jill A
authors: JA
authors: Rosenfeld
authors: Mindy P
authors: MP
authors: Dabell
authors: Justine
authors: J
authors: Coppinger
authors: Anne M
authors: AM
authors: Bandholz
authors: Jay W
authors: JW
authors: Ellison
authors: J Britt
authors: JB
authors: Ravnan
authors: Beth S
authors: BS
authors: Torchia
authors: Blake C
authors: BC
authors: Ballif
authors: Allan J
authors: AJ
authors: Fisher
mesh_terms: D000328:Adult; D001842:Bone and Bones / Q000002:abnormalities; D001921:Brain / Q000002:abnormalities; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D000013:Congenital Abnormalities / Q000000981:diagnostic imaging* / Q000235:genetics; D005260:Female; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D016142:Holoprosencephaly / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D046228:Microarray Analysis / Q000379:methods*; D009154:Mutation / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012189:Retrospective Studies; D016216:Ultrasonography, Prenatal