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.

 
We offer screening of the FMR1 gene to everyone including those who suspect having a premutation in the FMR1 gene. Furthermore, we perform 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 technique

Screening 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 range

Normal: 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%
 
Sample requirements
  • Blood (2-5 ml EDTA-blood
  • DNA (minimum 3 µg)
  • Saliva (minimum 2mL)
 
Test requirements
 
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

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