Array-CGH, Karyotype Analysis, and FISH
As obstetricians and perinatologists, we benefit from being aware of and fully informed about the evolving technology that continues to move the field of prenatal diagnosis forward. The array of current prenatal diagnostic tools includes both invasive and noninvasive techniques that enable parents to assess the genetic, chromosomal, and biochemical aspects of their fetus considerably before the time of viability.
Parents and their physicians are using this information to guide them in pursuing potential therapeutic applications and interventions or, in some cases, interruption of the pregnancy.
Now there is a new technique called array-based comparative genomic hybridization, or array-CGH, which is entering the prenatal arena with promises of more comprehensive and faster detection capabilities than we now are afforded with the two current “gold standard” techniques: microscopic karyotype analysis and rapid fluorescent in situ hybridization.
Array-CGH is far from perfect in evaluating chromosomal material. It can only detect instances where there is a significant addition or deletion of genetic material. And, of course, it can only evaluate those genes encoded on the array.
As with every other prenatal diagnostic tool developed to date, the future use of this new technique involves many questions, including which variants are normal as opposed to abnormal, the technique's potential role as a screening tool, and other often vexing ambiguities and issues. However, its use in prenatal diagnosis will build upon a body of national experience in the postnatal setting.
To familiarize us with the new technology and discuss its role in prenatal diagnosis, I have invited Dr. Karin J. Blakemore to serve as the guest professor of this month's Master Class.
Dr. Blakemore is the director of maternal-fetal medicine and the Prenatal Genetics Service at Johns Hopkins University School of Medicine in Baltimore—an institution that is gearing up to use array-CGH as part of its armamentarium for prenatal diagnosis.
She is joined by her colleague Denise Batista, Ph.D., who is an assistant professor in the Johns Hopkins department of pathology and codirector of the university's prenatal cytogenetics laboratory. Dr. Batista also serves as the director of the cytogenetics laboratory at the Kennedy Krieger Institute in Baltimore.
Key Points for Array-CGH
▸ Detects: Unbalanced rearrangements, aneuploidy, gains and losses of regions represented in the array.
▸ Won't detect: Balanced rearrangements, point mutations, (possibly) low-level mosaicism.
▸ Pick-up rate: Estimated as 5%–10% from postnatal studies of developmentally delayed/dysmorphic children.
▸ Confirmation: By FISH probes.
▸ Parental studies: Might be necessary to sort out normal variants versus clinically significant changes.
▸ Copy number variants: Might find copy number variants of unknown significance.
▸ Platforms: Several commercial and home-brew arrays available with different genomic coverage.
