Laboratory Blood Test Validated for Fragile X Syndrome

A laboratory blood test validated for fragile X syndrome holds promise for large-scale carrier and newborn testing.

Fragile X syndrome, which causes intellectual disability and other abnormalities, affects about 1 in 4,000 males in the United States. The syndrome also occurs in females, but causes less severe impairment. Caused by mutations of a gene called FMR1, it is relatively common in the population. Estimates vary, but 1 in 300 to 400 U.S. couples could be carriers of the abnormal genes.

Scientists have developed a new test for mutations of the FMR1 gene. Using polymerase chain reaction (PCR) technology to detect abnormalities called CGG repeats, the test detected not only full disease-causing mutations, but also milder gene expansions called premutations.

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 study of the new laboratory blood test for FMR1 mutations was performed by scientists at Quest Diagnostics (San Juan Capistrano, CA, USA) and published in the March 2010 issue of Genetics in Medicine. The authors found that there was a 100 % rate of agreement between the new test and the standard Southern blot test. Mutations were found in 6 of the 1,275 patients tested.

Despite its prevalence, population-based screening of potential carriers and newborns for mutations in the FMR1 gene has eluded scientists--largely due to technical limitations with high-throughput laboratory testing.

Women who are genetic carriers of Fragile X syndrome are frequently unaffected and can pass the syndrome to their offspring regardless of the father's genetic characteristics. In contrast, cystic fibrosis and Tay Sachs disease, both of which are widely screened for, occur only when both mother and father are carriers.

Currently available screening tests for fragile X syndrome are too expensive and time-consuming for use in routine screening of couples and newborns. As a result, testing is generally done only when there is some reason to suspect that the family is at high risk, such as already having a child with fragile X syndrome.

Dr. Feras M. Hantash, M.S., Ph.D., who led the study and colleagues at Quest Diagnostics, noted that in addition to medical and scientific questions, future studies would need to address the ethical and legal issues involved in screening for fragile X syndrome. "It certainly will be a challenge to educate the public about the complexities of fragile X testing," they wrote.

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