DNA microarrays: A promising new option for prenatal diagnosis

Array-based comparative genomic hybridization detects significantly more and smaller abnormalities than standard chromosome analysis. Already in limited use, the test may well replace karyotyping for prenatal diagnosis of genetic disorders.

Key Points

The syndromes that array-CGH can identify often lead to serious developmental abnormalities. Routine chromosome analysis cannot diagnose many of these syndromes because the extra or missing segment is too small to see (smaller than 4 to 5 megabases of DNA) on a standard karyotype (Figure 1A). A fluorescence in situ hybridization (FISH) test (Figure 1B) can detect such microdeletions and microduplications, but only for one or a few chromosomal regions at a time. Its use is restricted to situations in which a known deletion or duplication syndrome is suspected or when samples need to be tested rapidly for the most common trisomies ("aneuploidy FISH").

Because most deletion and duplication syndromes produce no specific prenatal symptoms, they are not suspected based on fetal U/S findings or abnormal maternal serum analyte levels. The only way to identify them consistently is to test for all or most of them each time prenatal diagnostic testing is done. Only array-CGH can achieve this in a single test.