FRAGILE X SYNDROME
Fragile X syndrome is characterized by developmental problems including learning disabilities, communication problems, social interactions, and cognitive impairment. This disorder affects males more severely than females since the mutation is inherited in an X-linked dominant pattern.
Fragile X syndrome is caused by mutation in the Fragile X Mental Retardation 1 (FMR1) gene. The protein encoded by FMR1 is important for maintaining a normal function of the synapses in the nervous system. Mutation in the FMR1 gene leads to an expansion of the CGG trinucleotide repeat. Normally the frequency of the CGG segment is 5-40 repeats in the FMR1 gene, but in affected people it is repeated more than 200 times. This leads to an inactivation or extreme reduced activity of the gene product. Occurrence of 55-200 repeats of the CGG triplet is defined as a premutation, and the affected people might have mild symptoms of the disorder.
Amplexa Genetics offers screening of the FMR1 gene to everyone including those who suspect having a premutation in the FMR1 gene. Furthermore, Amplexa Genetics performs genetic testing for the FMR1 gene mutation in women who like to undergo pregnancy with a sperm donor, and women who like to become an egg donor.
ANALYSIS TECHNIQUEScreening of FMR1 gene is performed by fragment length analysis technique, a powerful research tool that provides relative quantitation, sizing, and genotyping information, and enables a wide array of genetic analysis applications. The reagents provide a PCR-only approach based on Triplet Repeat Primed (TP-PCR) design, to amplify and detect all alleles, including full mutations.
REFERENCE RANGENormal: 5-44 CGG repeats
Grey zone: 45-54 CGG repeats
Pre-mutation: 55-200 CGG repeats
Full mutation: >200 CGG repeats
Limitation: Rare cases of FXS which is not caused by CGG repeats expansion will not be detected through this method.
ADVANTAGES USING TP-PCR
- Increased clinical accuracy compared to Southern Blot
- Low abundance total mutations are detected
- Increased resolution on female zygosity
- Repeats of AGG interruptions are detected
- Diagnostic Sensitivity of 100%; Diagnostic Specificity of 98.4% and Overall Accuracy of 99%
- Blood (2-5 ml EDTA-blood
- DNA (minimum 3 µg)
- Saliva (minimum 2mL)
TEST SPECIFICATIONSChemistry: CE IVD approved AmplideX® PCR/CE FMR1 from Asuragen
Hardware: SeqStudio Genetic Analyzer
Data processing: Data is analyzed in GeneMarker Software. A standard sample mixed by four samples from Coriell Institute, with 20, 29/31, 53, 118 repeats, is used.
Metrics: >95% sensitivity
By ordering an analysis at Amplexa Genetics A/S, the requester confirms to have obtained the necessary informed consent for the performance of the requested analyses and accepts Amplexa Genetics Terms and Conditions. A hard-copy requisition or an e-mail stating the specific study together with the receipt of a sample is considered an order to conduct the analysis.
From the day of order receipt, the turnaround time is five weeks.