Test Catalog

Test Id : FXS

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Fragile X Syndrome, Molecular Analysis, Varies

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Overview

Test Catalog

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

Confirmation of a diagnosis of fragile X syndrome, fragile X tremor/ataxia syndrome, or premature ovarian insufficiency caused by expansions in the FMR1 gene

 

Determination of carrier status for individuals with a family history of fragile X syndrome or X-linked intellectual disability

 

Prenatal diagnosis of fragile X syndrome when there is a documented FMR1 expansion in the family

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No
CULAF Amniotic Fluid Culture/Genetic Test Yes No
MATCC Maternal Cell Contamination, B Yes No
FUFXS Fragile X, Follow up Analysis No No
_STR1 Comp Analysis using STR (Bill only) No, (Bill only) No
_STR2 Add'l comp analysis w/STR (Bill Only) No, (Bill only) No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, fragile X follow-up analysis testing will be performed and charged dependent upon the reported gender of the individual and on the size of the CGG repeat found by polymerase chain reaction (PCR) analysis.

 

When sending in prenatal specimens: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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

Polymerase Chain Reaction (PCR)-Based Assay

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 Syndrome, Mol. Analysis

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

FMR1

Fragile X tremor ataxia syndrome

FXTAS

Martin-Bell Syndrome

FXPB

POF

Premature ovarian failure

POI

Premature ovarian insufficiency

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, fragile X follow-up analysis testing will be performed and charged dependent upon the reported gender of the individual and on the size of the CGG repeat found by polymerase chain reaction (PCR) analysis.

 

When sending in prenatal specimens: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing.

 

FMR1-methylation status cannot be assessed on chorionic villus specimens. Contact a molecular genetic counselor/consultant at 800-533-1710 to discuss the limitations of testing prior to sending a chorionic villus specimen for fragile X analysis.

Additional Testing Requirements

All prenatal specimens must be accompanied by a maternal blood specimen. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

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

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated

 

Prenatal Specimens

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

 

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 0.5 mL

Amniotic Fluid: 10 mL

Chorionic Villi: 5 mg

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

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

Confirmation of a diagnosis of fragile X syndrome, fragile X tremor/ataxia syndrome, or premature ovarian insufficiency caused by expansions in the FMR1 gene

 

Determination of carrier status for individuals with a family history of fragile X syndrome or X-linked intellectual disability

 

Prenatal diagnosis of fragile X syndrome when there is a documented FMR1 expansion in the family

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, fragile X follow-up analysis testing will be performed and charged dependent upon the reported gender of the individual and on the size of the CGG repeat found by polymerase chain reaction (PCR) analysis.

 

When sending in prenatal specimens: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

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 males and females. 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 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 patients 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.

 

Premature Ovarian Insufficiency:

Female patients with a premutation are at risk for increased follicular stimulating hormone (FSH) levels, early menopause, and POI. Penetrance and early onset of female reproductive symptoms correlates 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.

Normal alleles: 5-44 CGG repeats

Intermediate (grey zone) alleles: 45-54 CGG repeats

Premutation alleles: 55-200 CGG repeats

Full mutation alleles: >200 CGG repeats

An interpretive report will be provided.

 

Methylation status:

Unmethylated: < or =20%

Partially methylated: 21-69%

Fully methylated: > or =70%

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 our interpretation of results may occur if information given is inaccurate or incomplete.

 

Methylation status will not be assessed on chorionic villus specimens nor will it be assessed 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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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

A polymerase chain reaction (PCR)-based assay is used to detect expansions of a CGG trinucleotide tract in the 5'UTR of the FMR1 gene. Methylation status for large premutations (170+) and full mutation alleles is determined by capillary electrophoresis analysis of a PCR-amplified product from DNA that is treated with a methylation-sensitive restriction enzyme.(Grasso M, Boon EMJ, 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, Pergolizzi RG, Erster SH, Thibodeau SN: 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

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

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.

81243

88233 (if appropriate)

88240 (if appropriate)

88235 (if appropriate)

81265 (if appropriate)

81244 (if appropriate)

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
FXS Fragile X Syndrome, Mol. Analysis 81856-7
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.
52870 Result Summary 50397-9
52871 Result 81856-7
52872 Interpretation 69047-9
52873 Reason for Referral 42349-1
52874 Specimen 31208-2
52875 Source 31208-2
52876 Method 85069-3
52877 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