Fragile X Syndrome (FXS, OMIM # 309550) is an X-linked disease that is primarily based on the genomic expansion of a triplet of nucleotides (CGG), and aberrant methylation of the promoter region. The expansion is located in the 5’ untranslated region of the FMR1 gene (“Fragile X Mental Retardation 1) which is situated in the Xq27 region.Depending on the number of repetitions of this triplet, three categories can be established:
a) Number of repetitions from 6 to 45 or 55 and without methylation in the promoter of the gene, defines individuals with healthy alleles.
b) Number of repeats from 45 or 55 to 200 and often without aberrant gene methylation, defines the category of individuals with premutations (PM). In this case individuals are asymptomatic for disorders associated with FXS but can be associated with two clinical disorders: fragile X syndrome-associated tremor/ataxia (FXTAS) and fragile X-associated with primary ovarian insufficiency (FXPOI), the severity of which depends on the methylation state of the promoter. It is estimated that the incidence in the general population is 1 in every 130-250 females and 1 in every 250-810 males.
c) Number of repetitions over 200 and with aberrant methylation of the gene promoter defines individuals with full mutations, which results in the elimination of gene expression in the human brain, and is associated with mental retardation, autism, and mental and emotional changes. It has a striking phenotype consisting of large ears and a prominent jaw, with an incidence of 1 in 4000 males and 1 in 8000 females. However, there are some rare cases where large unmethylated expansions are present in normal patients. Moreover, CGG repeats in premutated alleles are unstable and may increase in size from generation to generation by maternal transmission, resulting in a generation with a fully mutated allele.
Adellgene® Fragile X Screening is a diagnostic kit which detects the number of CGG triplet repeats (cytosine-guanine-guanine) in the 5’ untranslated region of the gene for fragile X men-tal retardation (“Fragile X mental retardation-1”: FMR1). The technology is based on the polymerase chain reaction (PCR) amplification of genomic DNA, ex-tracted and purified from peripheral blood, followed by fluorescence analysis of the size of the PCR fragments obtained by a genetic analyzer and conversion of that size into the relevant number of CGG repeats.