Test Catalog

Test Id : FUFXS

Fragile X, Follow-up Analysis

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirming the methylation status of the repeat expansion allele in the FMR1 gene, to aid the diagnosis of FMR1-related disorders 

Method Name
A short description of the method used to perform the test

Only orderable as a reflex. For more information see FXS / Fragile X Syndrome, Molecular Analysis, Varies.

 

Methylation Sensitive Polymerase Chain Reaction (PCR) Fragment Analysis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Fragile X, Follow up Analysis

Aliases
Lists additional common names for a test, as an aid in searching

FXFU

Specimen Type
Describes the specimen type validated for testing

Varies

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Only orderable as a reflex. For more information see FXS / Fragile X Syndrome, Molecular Analysis, Varies.

 

No additional specimen is required. Lab will utilize specimen they already have in the lab for this test.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Confirming the methylation status of the repeat expansion allele in the FMR1 gene, to aid the diagnosis of FMR1-related disorders 

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Fragile X syndrome is an X-linked disorder with variable expression in male and female patients. In greater than 99% of affected individuals, it is caused by an expansion of the CGG trinucleotide repeat in the 5'UTR (untranslated region) of the FMR1 gene located on the X chromosome. This trinucleotide repeat is polymorphic in the general population, with the number of repeats ranging from 5 to 44. These normal alleles are passed from generation to generation, with the number of repeats remaining constant. Small expansions, called premutations, range from 55 to 200 CGG repeats. Individuals with a premutation do not exhibit features of fragile X syndrome but are at risk for other FMR1-related disorders, such as fragile X tremor/ataxia syndrome (FXTAS) and premature ovarian insufficiency (POI). Transmission of a premutation by a man to his daughter usually results in little or no change in the CGG repeat number. Transmission of a premutation by a woman to her son or daughter usually results in further expansion, either to a larger premutation or a full mutation. The risk for a woman with a premutation to have a child affected with fragile X syndrome by expansion to a full mutation increases with the number of CGG repeats in the premutation. Full mutations are typically greater than 200 repeats long and are associated with abnormal methylation of a region adjacent to the FMR1 gene. This is thought to interfere with normal FMR1 gene expression, resulting in fragile X syndrome. There are multiple clinical phenotypes associated with expansion (premutations and full mutations) in the FMR1 gene.

 

Fragile X Syndrome:

Approximately 1 in 4000 individuals are affected with fragile X syndrome. Most affected male patients exhibit moderate intellectual disability, with affected female patients having milder, if any, cognitive deficiency. Neuropsychiatric diagnoses, such as autism spectrum and anxiety disorders, are common. Characteristic physical features include a long face with a prominent jaw, protruding ears, connective tissue abnormalities, and large testicles in postpubertal male patients.

 

Fragile X Tremor/Ataxia Syndrome:

FXTAS is a neurodegenerative disorder that is clinically distinct from fragile X syndrome. Both male and female patients with a premutation are at risk for FXTAS. However, the disorder is much less common and milder in clinical presentation than fragile X syndrome and shows a later age of onset in female patients. Clinical hallmarks of the disorder include intention tremor, gait ataxia, dementia, and neuropsychiatric symptoms. The risk for FXTAS increases as the number of CGG repeats increases, and the majority of individuals with FXTAS have CGG repeat expansions of 70 or more. Penetrance of clinical symptoms is associated with increasing age, with the majority of affected men showing symptoms between age 70 and 90 years.

 

Premature Ovarian Insufficiency:

Female patients with a premutation are at risk for increased follicular stimulating hormone levels, early menopause, and POI. Penetrance and early onset of female reproductive symptoms correlate with increasing size of the CGG repeat and reaches its highest penetrance at approximately 80 to 90 repeats. Of note, penetrance remains stable or may even decrease at approximately 100 repeats. There is no risk for increased penetrance of the POI phenotype due to maternal or paternal inheritance of the expanded CGG repeat.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Only orderable as a reflex. For more information see FXS / Fragile X Syndrome, Molecular Analysis, Varies.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

For predictive testing, it is important to first document the presence of CGG-repeat amplification in the FMR1 gene in an affected family member to confirm that molecular expansion is the underlying mechanism of disease in the family.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.

 

Methylation status will not be assessed on chorionic villus specimens or if the reported sex is female.

 

Less than 1% of individuals clinically diagnosed with fragile X syndrome do not have the CGG expansion-type mutation. These individuals may have a different type of variant within the FMR1 gene (eg, deletion or point alteration).

 

Due to incomplete penetrance and variable expression of the FMR1 expansion, this test is not reliable for prenatal assessment of disease severity.

 

The absence of an expansion in the FMR1 gene does not eliminate the diagnosis of other inherited disorders that have overlapping clinical features with fragile X syndrome, fragile X tremor/ataxia syndrome, or premature ovarian insufficiency.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Jacquemont S, Hagerman RJ, Hagerman PJ, Leehey MA: Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. Lancet Neurol. 2007 Jan;6(1):45-55

2. Finucane B, Abrams L, Cronister A, Archibald AD, Bennett RL, McConkie-Rosell A: Genetic counseling and testing for FMR1 gene mutations: practice guidelines of the National Society of Genetic Counselors. J Genet Couns. 2012 Dec;21(6):752-60

3. Monaghan KG, Lyon E, Spector EB: ACMG standards and guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics. Genet Med. 2013 Jul;15(7):575-586

4. Biancalana V, Glaeser D, McQuaid S, Steinback P: EMQN best practice guidelines for the molecular genetic testing and report of fragile X syndrome and other fragile X-associated disorders. Eur J Hum Genet. 2015 Apr;23(4):417-425. doi: 10.1038/ejhg.2014.185

Method Description
Describes how the test is performed and provides a method-specific reference

Methylation for premutation and full mutation alleles is determined by capillary electrophoresis analysis of a polymerase chain reaction-amplified product from DNA that is treated with a methylation-sensitive restriction enzyme.(Grasso M, Boon EM, Filipovic-Sadic S, et al: A novel methylation PCR that offers standardized determination of FMR1 methylation and CGG repeat length without southern blot analysis. J Mol Diagn. 2014 Jan;16(1):23-31; Snow K, Doud LK, Hagerman R, et al: Analysis of a CGG sequence at the FMR-1 locus in fragile X families and in the general population. Am J Hum Genet. 1993 Dec;53(6):1217-1228)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

8 to 10 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81244

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
FUFXS Fragile X, Follow up Analysis No LOINC Needed
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
52421 Comment 48767-8
52422 Specimen 31208-2
52423 Source 31208-2
52424 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports