Fragile X syndrome is an X-linked recessive disorder that mainly affects male carriers; however, it has a broad range of signs and symptoms based on who carries the gene and what type of expansion or methylation is present. Fragile X syndrome (FXS) is a trinucleotide repeat expansion disorder caused predominantly by the expansion of the CGG sequences in the 5’ untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene (on the long arm of the X chromosome), which may reduce its expression or inactivate the gene. FMR1 gene inactivation leads to non-expression of the fragile X Mental Retardation Protein (FMRP), which is predominantly expressed in neurons and is involved in mRNA stability, transport, and translation. The shutdown of the FMRP production results in the manifestation of FXS, which is the most prevalent type of heritable intellectual disability in men.

The clinical manifestation of the FXS is usually determined by the genotypes of the FMR1 alleles. It is categorized into normal, intermediate, premutation, and full mutation genotypes based on the number of repeat expansions. Individuals with full mutations (>200 CGG repeats) often present so-called classic FXS, characterized by mental retardation, autism, and emotional and psychiatric challenges. Carriers with premutation alleles (55 to 200 repeats) usually do not develop FXS; however, they may be at risk of developing other adverse health problems in adulthood, such as tremor/ataxia syndrome (FXTAS) in both genders or fragile X-associated primary ovarian insufficiency (FXPOI) in females. Importantly, female premutation carriers are at risk of transmitting a full mutation allele to their children. Indeed, it has been shown that repeat expansion causing a premutation gene to convert to a full mutation is mainly seen in females carrying the premutation gene who have full mutation offspring. Thus, a wide spectrum of people of all ages with various mental and physical health concerns may be impacted by fragile X syndrome and related illnesses. Genetic testing is crucial to establish the clinical diagnosis of FXS and its related illnesses and to identify carriers of expanded premutation alleles in family planning and genetic counselling. Therefore, result interpretation and counselling must be adjusted to these facts. We highly recommend users of the GT FXS Detector kit to follow the EMQN Best Practice Guideline, the ACGS Practice Guidelines for Molecular Diagnosis of Fragile X, and the ACMG Standards and Guidelines for Fragile X Testing for result interpretation and counselling.

Genetek has developed GT FXS Detector kit to accurately determine the number of CGG repeats in normal and affected DNA samples. The kit enables the user to accurately determine the number of CGG repeats for carrier screening, confirming Fragile X in affected cases as well as prenatal diagnosis. Unique gradient colored panel will help the user to visualize the result even before allele numbering. However, allele calling is aided by incorporating bins into the panel. All supporting files can be downloaded from this website.

GT FXS Detector is simple to use, and PCR product must be run on a capillary electrophoresis machines  such as 3130/xl or 3500/xL Genetic Analyzer from Thermo Fisher or Compact Spectrum CE System from Promega.

Premium Features

·For rapid and accurate detection of CGG repeat numbers in the FMR1 gene using triplet PCR.

·Easy to interpret results by having a special panel showing the repeat range and severity of the disease based on repeat numbers.

·Allele calling is aided by incorporation of bins in the panel.

·Easy to use mix and rapid sample to PCR and result.

For research use only.

Markers

The panel below shows repeat numbers and the severity of the disease. Colors indicate normal (green) to severe disease (dark red) with bins for quick and accurate repeat numbers.

Repeat Number Interpretation

Table for interpreting GT FXS Detector results. Size range, repeat numbers, health condition are given.

Sample Profile

Compatibility

This kit is compatible with 5 dyes capillary electrophoresis system such as with ABI 3130/xl, 3500/xL , and SeqStudio Genetic Analyzers with either 30, 50, or 80 capillaries.

This kit can be used on various sources of DNA including DNA extracted from various sources

Kit Content

The kit contains all the necessary reagents and buffers for a triplet PCR  (Primer mix, PCR buffer, GT Taq DNA Pol in Box A). Also, the kit comes with GT1200 size standard as well as GTM5 v2 Matrix Standard for calibrating the Genetic Analyzer (Box B).