The Fragile X DNA Test The fragile X mutation Within the fragile X (FMR1) gene is a stretch of repeated trinucleotides with the sequence CGG. The nucleotides C and G are two of the four building blocks of DNA. Among people without the fragile X mutation, the number of these "CGG repeats" varies from 6 to about 40. The fragile X mutation involves
an expanded number of the CGG repeats. Expansions with between 55 and 200 repeats, called premutations, are seen in unaffected carriers. Between 40 and 55 repeats is considered a 'grey zone' where normal and premutation size ranges overlap. Expansions with more than 200 repeats, called full mutations, are associated with methylation which "turns off" the gene. Males with a full mutation are
affected with fragile X syndrome. Approximately 50% of females with a full mutation have cognitive impairment and of the 50% with a normal IQ, 60% have some emotional or behavioral effects. An FMR1 premutation tends to increase in size when transmitted from a female to her children, and the risk for expansion to a full mutation increases with the size of the premutation. (For a review of the molecular biology of the fragile X mutation see Brown et al, 1996).
The concept of the test Testing for the fragile X mutation is based primarily on measuring the length of the FMR1 gene region containing the CGG repeat stretch and then calculating the CGG repeat number. Analysis of the gene's methylation status (ie. whether the gene is turned 'off ' or 'on') is often performed simultaneously. Categorization of the mutation type is based on CGG repeat number and in some
cases also on the methylation status of the gene. Methylation information is useful for delineating premutations from full mutations when the repeat number is intermediate (~150-250) and can have prognostic value when a full mutation is methylated in only a small percentage of cells. (For a review of fragile X analysis, see Warren et al, 1994) Southern blot analysis Polymerase Chain Reaction (PCR) Annette K. Taylor, M.S., Ph.D.
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