DNA Test IDs Genetic Causes of Fetal Illness.

• Position: EXOME SEQUENCING

The promise of high-throughput DNA-sequencing technologies to improve prenatal diagnosis and pregnancy outcomes for women who have experienced an abnormal prenatal ultrasound has been shown via a study--led by researchers at the University of California, San Francisco--published in The New England Journal of Medicine.

"The cause of most cases of NIHF [non-immune hydrops fetalis] is not identified with standard testing but, when we apply exome sequencing, we find a genetic diagnosis in nearly 30% of cases of previously unknown cause," says study leader and corresponding author Teresa Sparks, assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences.

NIHF affects about one in every 1,700 to 3,000 pregnancies in the U.S. and is associated with high risks of stillbirth, preterm birth, neonatal death, and other complications. Although NIHF often leads to death, identifying the precise genetic cause is critical, as associated outcomes vary widely in severity.

NIHF can be a manifestation of many genetic diseases, but evidence of abnormal fluid accumulation in the fetus detected through an ultrasound exam--whether it occurs under the skin, in the abdomen, or around the heart or lungs--does not pinpoint an underlying cause.

Participants in the study were referred from throughout the U.S. after NIHF was identified with prenatal ultrasound but no underlying genetic disease was found using long-established methods for detecting genetic abnormalities. These traditional genetic tests--karyotype and chromosomal microarray analysis--detect large abnormalities in chromosomes, not disorders caused by a defect in a single gene as are identified with exome sequencing.

Exome sequencing is the complete spelling out of the genetic code for DNA segments within the genome that serves as the blueprints for proteins. This has become possible to perform quickly and accurately in recent years, thanks to the continual refinement of technology that can...