Non-targeted whole genome 250K SNP array analysis as replacement for karyotyping in fetuses with structural ultrasound anomalies: evaluation of a one-year experience

Prenat Diagn. 2012 Apr;32(4):362-70. doi: 10.1002/pd.2948.

Abstract

Objective: We evaluated both clinical and laboratory aspects of our new strategy offering quantitative fluorescence (QF)-PCR followed by non-targeted whole genome 250K single-nucleotide polymorphism array analysis instead of routine karyotyping for prenatal diagnosis of fetuses with structural anomalies.

Methods: Upon the detection of structural fetal anomalies, parents were offered a choice between QF-PCR and 250K single-nucleotide polymorphism array analysis (QF/array) or QF-PCR and routine karyotyping (QF/karyo).

Results: Two hundred twenty fetal samples were included. In 153/220 cases (70%), QF/array analysis was requested. In 35/153 (23%), an abnormal QF-PCR result was found. The remaining samples were analyzed by array, which revealed clinically relevant aberrations, including two known microdeletions, in 5/118 cases. Inherited copy number variants were detected in 11/118 fetuses, copy number variants with uncertain clinical relevance in 3/118 and homozygous stretches in 2/118. In 67/220 (30%) fetuses, QF/karyo was requested: 23/67 (34%) were abnormal with QF-PCR, and in 3/67, an abnormal karyotype was found.

Conclusion: Even though QF/array does not reveal a high percentage of submicroscopic aberrations in fetuses with unselected structural anomalies, it is preferred over QF/karyo, as it provides a whole genome scan at high resolution, without additional tests needed and with a low chance on findings not related to the ultrasound anomalies.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Chromosome Disorders / genetics*
  • Congenital Abnormalities / diagnostic imaging
  • Congenital Abnormalities / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Karyotyping / methods*
  • Karyotyping / statistics & numerical data
  • Molecular Diagnostic Techniques / methods
  • Molecular Diagnostic Techniques / statistics & numerical data
  • Oligonucleotide Array Sequence Analysis / methods
  • Oligonucleotide Array Sequence Analysis / statistics & numerical data
  • Polymerase Chain Reaction / methods*
  • Polymerase Chain Reaction / statistics & numerical data
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Ultrasonography, Prenatal / methods*