A major advance in fragile X testing that could alter the feasibility of population screening in a major way was described in late March at the meeting of the American College of Medical Genetics by Charles Strom, MD, PhD, FAAP, FACMG, HCLD, medical director of the Genetic Testing Center of Quest Diagnostics Nichols Institute.
“We have invented a new technology—capillary Southern analysis,” Dr. Strom says. “It provides accurate sizing across the entire spectrum of [CGG] repeats and is 100 percent sensitive in detecting both males and females with pre- and full mutations, as well as mosaicism.” In addition, the new assay is entirely automatable and high throughput and has a rapid turnaround time—less than one week.
Realization of the new assay took four years. “We had to take a technology that was developed for another application—a Beckman instrument for capillary zone electrophoresis—and adapt it for a new purpose,” Dr. Strom says. The principles of restriction digestion, size separation, and gene-specific identification are the same as in the standard fragile X assay. After a standard Southern enzyme digestion, samples are run on the capillary electrophoresis instrument, which collects fractions by size. PCR is done, not across triplet repeats but on a flanking region, Dr. Strom explains. Fractions are then examined for fragile X-specific fragments. The new technology and its validation will be described in detail in the April issue of the ACMG’s journal, Genetics in Medicine.
The new assay will go live in April and will initially be offered by Quest Diagnostics. But Dr. Strom says Quest is hoping eventually to license it to other laboratories. “We want eventually to get some sort of population screening accepted,” he says. The new technology will enable the debate about screening to move beyond theory and into practice, in his view. “Before, you couldn’t do screening scientifically,” he says. “Now the scientific barrier has been put away and it is time to do pilot studies.”
“This new assay may change the face of clinical fragile X testing in the very near future,” agrees Jean Amos Wilson, PhD, scientific director of human genetics at Focus Diagnostics. “It may pave the technical path toward fragile X carrier screening.”
William Check is a medical writer in Wilmette, Ill.