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.
Click here for the OMIM summary on this condition.
Please note that AFF2 and FMR2 are the same gene. This test is therefore a single-gene test.
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
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%
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, 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.
- Prenatal testing is available to adult females who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.