Fragile X syndrome (FRAXA & FRAXE)

Fragile X syndrome is the most common inherited form of mental retardation and in particular of X-linked mental retardation-XLMR, which is expressed almost exclusively in males. Because the region responsible for the syndrome is located on the X chromosome, the disease is X-linked (expressed primarily in males who have only one X chromosome), while females, carrying two X chromosomes, are carriers and are usually not affected. As the name implies, the syndrome is directly related to increased fragility of the Xq27.3 region of the X chromosome. Less than 1/3 of female carriers exhibit mild to moderate mental retardation, which in most cases they go unnoticed. The frequency of the syndrome is about 1/5,000 male births, while the frequency of female carriers is about 1/250 – 1/500.

The underlying genetic cause is due to an abnormal expansion of the number of the triplet of bases (CGG) of the FMR1 gene, which is located in the FRAXA region on the Xq27.3 chromosomal region. There is also a small number of patients with moderate mental retardation, with a similar expansion of (CGG) repeats of the FMR2 gene, located in the nearby FRAXE locus of the X chromosome. Generally, (CGG) triplet repeats greater than 200 are considered pathogenic-full mutations, leading to the expression of the disease.

The testing methodology we apply combines specific multiplex fluorescent PCR reactions, triplet-repeat PCR and MS-MLPA, allowing us to detect the exact number of (CGG) triplet repeats and the presence of >200 (CGG) repeat expansions in both the FMR1 and FMR2 genes (FRAXA and FRAXE), as well as the methylation status of the FMR1 gene, providing an overall assessment of the genetic defects associated with the syndrome.

InterGenetics participates with great success in the external quality assessment scheme organized by the European Molecular Genetics Quality Network (EMQN), which is periodically applied for Fragile X syndrome