title: Identification of submicroscopic chromosomal aberrations in fetuses with increased nuchal translucency and apparently normal karyotype.
abstract: OBJECTIVE
  Fetal nuchal translucency (NT) is assessed by ultrasonography as a screening tool for aneuploidy at 11 to 13 + 6 weeks' gestation. Fetuses with increased NT but apparently normal karyotype are still at higher risk of structural abnormality and a range of genetic syndromes, which may be related to major and submicroscopic chromosomal abnormalities. The aim of this study was to report the prevalence of submicroscopic chromosomal abnormalities in a cohort of apparently euploid fetuses that presented with increased NT.
  
  
  METHODS
  DNA was extracted from stored chorionic villus samples from fetuses found to have increased NT (> 3.5 mm) during first-trimester screening. These samples were examined by microarray-based comparative genomic hybridization (aCGH) using a 44K oligonucleotide array specifically constructed for prenatal screening. Variations in copy number (CNVs) were reported after excluding known non-pathogenic variants and after validation with multiplex ligation-dependent probe amplification (MLPA) or real-time quantitative polymerase chain reaction (qPCR). The prevalence of pathogenic CNVs is reported and the association with NT and other ultrasound findings described.
  
  
  RESULTS
  CNVs were reported in 6/48 (12.5%) cases by aCGH and the microdeletions or microduplications ranged from 1.1 to 7.9 Mb. Five of these were validated by MLPA/real-time qPCR and four (8.3%) were considered to be pathogenic and clinically significant. The incidence of pathogenic CNVs was 20.0% (2/10) among those cases with other sonographic anomalies and 5.3% (2/38) among those without.
  
  
  CONCLUSIONS
  aCGH allows detection of submicroscopic chromosomal abnormalities, the prevalence of which may be increased in fetuses with NT > 3.5 mm and an apparently normal karyotype.
authors.affiliation: Fetal Medicine Unit, Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR.
authors.forename: T Y
authors.initials: TY
authors.lastname: Leung
authors.forename: I
authors.initials: I
authors.lastname: Vogel
authors.forename: T K
authors.initials: TK
authors.lastname: Lau
authors.forename: W
authors.initials: W
authors.lastname: Chong
authors.forename: J A
authors.initials: JA
authors.lastname: Hyett
authors.forename: O B
authors.initials: OB
authors.lastname: Petersen
authors.forename: K W
authors.initials: KW
authors.lastname: Choy
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations / Q000196:embryology*; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D005865:Gestational Age; D006801:Humans; D007621:Karyotyping; D048208:Nuchal Translucency Measurement / Q000379:methods; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011256:Pregnancy Outcome; D012307:Risk Factors; D016216:Ultrasonography, Prenatal