FRAGILE X SYNDROME

Fragile X syndrome is a genetic disorder characterized by developmental problems including learning disabilities, communication problems, social interactions, and cognitive impairment. This disorder affects both males and females, however, it 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 which encodes the Fragile X Mental Retardation Protein (FMRP). This protein 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 in the 5’ UTR of the gene. 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 a silencing or truncation of the gene product and thereby an absence or severely reduced expression of the FMRP in the nervous system. Occurrence of 55-200 repeats of the CGG triplet is defined as a premutation in the FMR1 gene, and the affected people might have mild symptoms of the disorder. Premutation in the carrier will develop to a full mutation in the next generation.

ANALYSIS TECHNIQUE

Fragment length analysis. The reagents provide a PCR-only approach based on Triplet Repeat Primed PCR (TP-PCR) design to amplify and detect all alleles, including total mutations.

REFERENCE RANGE

Normal: Between 5-44 CGG repeats

Grey zone: Between 45-54 CGG repeats

Pre-mutation: Between 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%

SAMPLE REQUIREMENTS

  • Blood (2-5 ml EDTA-blood
  • DNA (minimum 3 µg)
  • Saliva (minimum 2mL)

TEST SPECIFICATIONS

Chemistry: 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 

 

RESUME

Fragile X syndrome is a genetic disorder characterized by developmental problems including learning disabilities, communication problems, social interactions, and cognitive impairment. Fragile X syndrome is caused by mutation in the Fragile X Mental Retardation 1 (FMR1) gene which encodes the Fragile X Mental Retardation Protein (FMRP). This protein is important for maintaining a normal function of the synapses in the nervous system.

 

Amplexa Genetics offers genetic testing for 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 a pregnancy with a sperm donor, and women who like to become an egg donors. Testing for fragile X syndrome is also included in our more expansive X-Linked Carrier test.

TERMS

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.