Disease Background

• Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and autism.  This x-linked disorder is caused by a full mutation expansion (>200 CGG repeats) within the FMR1 gene
  • Affects approximately 1 in 4,000 males and 1 in 8,000 females in the United States.
• Carrier screening for fragile X syndrome is recommended by the American College of Obstetricians and Gynecologists (ACOG)
  • Approximately 1 million women are estimated to be fragile X carriers – yet most may be unaware of their carrier status.
• Testing for fragile X syndrome and its associated disorders (FXTAS, FXPOI) necessitates the accurate sizing of FMR1 CGG repeats across distinct clinical categories.
  • Normal (5-44 repeats)
  • Intermediate (45-54 repeats)
  • Premutation (55-200 repeats)
  • Full mutation (>200 repeats)

Features & Benefits

The AmplideX Fragile X Dx and Carrier Screen Kit makes the diagnosis and screening of fragile X syndrome rapid, robust, and reliable.  The assay also provides access to Asuragen’s Xpansion Interpreter service for the accurate detection of AGG interruptions in the CGG repeat sequence, which allows for a more refined risk assessment for select premutation carriers. To learn more about this offering, click here.

Reduced ComplexityEase-of-data analysis and reporting

• Cleared test supports rapid assay validation
• Implementation of proprietary PCR solution for amplifying GC-rich regions
• Clinically-validated AmplideX PCR/CE Fragile X Reporter software automates sample genotyping

Optimized WorkflowReduces valuable operator hands-on-time and overall turnaround time

• A single multi-allele control provides a peak in every clinical category and can be used as positive control
• Up to 50-fold reduction in Southern blot analysis
• End-to-end solution for FMR1 analysis including all necessary reagents and software

Quality ResultsHighly-sensitive, precise, and accurate assessment of allele size for screening and diagnosis

• Detection of challenging allele expansions — including low abundance full mutation size mosaics — provides more sensitive and accurate diagnosis of Fragile X
• Rapid and accurate sizing enables high throughput identification of premutation carriers; access to Xpansion Interpreter® can further refine the risk to full mutation expansion
• Proven performance of technology as indicated by over 100 peer-reviewed publications

Product Description

• Accurately detects and sizes alleles ≤200 CGGs and detects alleles >200 CGGs including mosaic alleles present at low allele fraction (Figure 1).
• Clearly resolves zygosity via visual repeat primer pattern (Figure 2).
• High percent agreement between AmplideX Fragile X Dx and Carrier Screen Kit and Southern blot for both diagnosis of fragile X syndrome (Table 1) and screening for fragile X carriers (Table 2).
• Detects low percent mosaic alleles in broad spectrum of different major allele backgrounds (Table 3).
• DNA-to-results in just one day (Figure 3).

Figure 1. Example of major premutation (PM) allele (90 CGG) with full mutation (FM) mosaic allele (>200 CGG) at 5% mosaic allele fraction

Figure 2. Clear, visual resolution of zygosity via repeat primer (“stutter”) peak pattern. A) Shows a sample with a homozygous 30/30 CGG call. No stutter pattern is present after the gene-specific peak, indicating no further peaks are present.  B) Shows a heterozygous sample with a heterozygous 24/> 200 CGG call. There is a marked stutter peak pattern after the first gene-specific peak (24), indicating the presence of another gene-specific peak (>200).

Table 1. Full Mutation Positive vs. Full Mutation Negative assessment comparing the AmplideX^® Fragile X Dx & Carrier Screen Kit with Southern Blot Analysis

Table 2. Premutation vs. Normal or Intermediate assessment comparing the AmplideX Fragile X Dx & Carrier Screen with Southern Blot Analysis

Table 3. Limit of Detection for mosaic alleles in different major allele backgrounds

Figure 3. Workflow for the AmplideX^® Fragile X Dx & Carrier Screen Kit

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