In samples with previously identified FMR1 mutations, the new PCR test showed a distinct "stutter" pattern whenever a full or partial mutation was present. It was also capable of detecting FMR1 "mosaics," which can be difficult to detect with standard approaches. The test was further evaluated in a series of 1,275 blood samples submitted for fragile X testing. The results showed a 100 percent rate of agreement between the new test and the standard "Southern blot" test. Mutations were found in 6 of the 1,275 patients tested.

With further study, the new PCR test may open the way to more widespread testing for fragile X mutations. This could include routine screening of newborns, as the test can detect FMR1 mutations in standard newborn blood spots. Abnormal screening results would require further diagnostic evaluation, including the standard Southern blot test. The researchers estimate that the screening test could reduce the number of Southern blot tests performed by 99 percent, thus saving considerable time and money.

More research will be needed before the ACMG and other organizations issue official recommendations on prenatal screening. In addition to medical and scientific questions, studies will need to address the ethical and legal issues involved with screening for fragile X syndrome. "It certainly will be a challenge to educate the public about the complexities of fragile X testing," Dr. Hantash and colleagues write.

Source: American College of Medical Genetics