From Discovery to Commercialisation of Fragile X Syndrome (FXS) PCR Assay
Fragile X Syndrome (FXS) is the most common known cause of mental retardation and developmental disabilities. It is a single gene disorder on the X chromosome that occurs in both males and females. FXS shuts down the gene responsible for producing FMRP (Fragile X Mental Retardation Protein), a protein essential for normal brain function.
FXS is associated with an expansion mutation within a segment of the X chromosome's FMR1 gene that contains a series of trinucleotide (CGGn) repeats. Alleles from unaffected (normal) individuals contain between 5 and 44 copies of the CGG repeat. In most cases, parents with a normal copy of the FMR1 gene pass it along to their offspring. However, due to unknown causes, this region can become progressively unstable, resulting in an increased number of CGG repeats over several generations. CGG repeats between 55 and 230 are classified as premutation. Premutation is unstable and are likely to expand to full mutation in the following generations. The longer the repeat, the less stable it is. Mothers with premutations (carriers) can have affected full mutation sons.
As one of the more difficult & labour-intensive tests to perform Abbott and Celera recognised a need for a simple, standardised routine method that was capable of detecting large-sized repeats and differentiating normal homozygote females. Using capillary electorphoresis this assay can size up to 230 CGG repeats.