Molecular carrier testing for the fragile X syndrome: Issues for genetic counselors

Molecular analysis of the fragile X (FMR-1) gene identifies female fragile X carriers, but appropriate genetic counseling can only be provided if the limitations of the testing methods are understood. Molecular analysis of this gene is achieved with both the polymerase chain reaction (PCR) and Southern blot techniques. PCR is faster and can determine the actual number of CGG repeats, which modifies genetic counseling substantially. However, for a sizeable percentage of women, PCR alone is not conclusive, and Southern analysis is necessary to complete the study. While this procedure takes longer, it is usually conclusive. Women who present for genetic counseling and carrier testing in the second trimester of pregnancy need this information quickly, and for them the turn-around time is paramount. It is critical that genetic counselors understand these methods so that they can educate their clients and facilitate appropriate follow-up.