Test Code: 2763

FRAXE Syndrome: AFF2 Gene Sequencing
Test Code: 2763
Turnaround time: 5 weeks


In patients who have the cytogenetic changes of fragile X syndrome but lack the molecular changes characteristic of that disorder (i.e., are
FMR1-mutation negative), a second site of fragility, symbolized FRAXE, has been demonstrated to be expanded. Data suggests that an etiologic relationship may exist between FRAXE and nonspecific X-linked intellectual disability. Loss of expression of the gene AFF2 has been correlated with FRAXE expansion. Sequence analysis and deletion/duplication analysis are also available to identify mutations in the AFF2 gene.

For patients with suspected FRAXE syndrome, repeat expansion testing and methylation analysis are recommended as the first step in mutation identification. For patients in whom mutations are not identified, full gene sequencing and deletion/duplication analysis are also available.


This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of FRAXE syndrome
  • Carrier testing in adult females with a family history of FRAXE syndrome


Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not mean to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.


Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s biochemical phenotype.

Analytical Sensitivity: ~99%


Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Submit copies of diagnostic biochemical test results with the sample, if appropriate.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed by another third party provider, please submit a copy of the sequencing report with the test requisition.


• Repeat expansion testing and methylation analysis are available and are strongly recommended as the first step in mutation identification. Deletion/duplication analysis of the AFF2 gene by CGH array is available for those individuals in whom sequence analysis is negative.
• A CGH array-based test for deletion/duplication analysis of 109 different X-linked intellectual disability genes is available.
• Testing for fragile X syndrome at the FRAXA site is available by repeat expansion/methylation analysis, FMR1 sequencing, and FMR1 deletion/duplication analysis.
• Custom diagnostic mutation analysis is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.