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Test ID: FXS Fragile X Syndrome, Molecular Analysis

Useful For

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

              

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

 

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

Reflex 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

Testing Algorithm

When this test is ordered, fragile X follow-up analysis testing will be performed and charged dependent upon on the size of the CGG repeat found by PCR analysis.

 

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test 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.

Method Name

Polymerase Chain Reaction (PCR)-Based Assays
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)

Reporting Name

Fragile X Syndrome, Mol. Analysis

Specimen Type

Varies


Specimen Required


Forms:

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

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

3. If not ordering electronically, complete, print, and send a Neurology Test Request Form-General (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)

 

Specimen preferred to arrive within 96 hours of collection.

 

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.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. CST on Friday in order to be processed appropriately. All prenatal specimens must be accompanied by a maternal blood specimen. Order MATCC / Maternal Cell Contamination, Molecular Analysis on the maternal specimen.

 

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

Additional Information: FMR1-methylation status cannot be assessed on chorionic villus specimens. Contact a molecular genetic counselor/consultant at Mayo Medical Laboratories at 1-800-533-1710 to discuss the limitations of testing prior to sending a chorionic villus specimen for fragile X analysis.

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


Specimen Minimum Volume

Blood: 0.5 mL/Amniotic Fluid: 10 mL/Chorionic Villi: 5 mg

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Clinical Information

Fragile X syndrome is an X-linked disorder with variable expression in males and females. It is caused by an expansion of the CGG trinucleotide repeat in 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, most often range from 59 to 200 CGG repeats. Premutation carriers 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 failure (POF). Transmission of a premutation by a male to his daughter usually results in little or no change in the CGG repeat number. Transmission of a premutation by a female to her son or daughter usually results in further expansion, either to a larger premutation or a full mutation. The risk for a female premutation carrier 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 can be 200 to thousands of 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 1/4000 individuals (male and female) are affected with fragile X syndrome. Most affected males exhibit moderate mental retardation, with affected females 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 males.

 

Fragile X Tremor/Ataxia Syndrome (FXTAS):

FXTAS is a neurodegenerative disorder that is clinically distinct from fragile X syndrome. Both male and female premutation carriers are at risk for FXTAS. However, the disorder is much less common, milder in presentation, and shows a later age of onset in females. 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 males showing symptoms between age 70 and 90.

 

Premature Ovarian Failure (POF):

Female premutation carriers are at risk for increased follicular stimulating hormone (FSH) levels, early menopause, and POF. 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 actually remains stable or may even decrease at approximately 100 repeats. There is no risk for increased penetrance of the POF phenotype due to maternal or paternal inheritance of the expanded CGG repeat.

Reference Values

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.

Interpretation

An interpretive report will be provided.

Clinical Reference

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;6(1):45-55

2. Mc-Conkie-Rosell A, Finucane B, Cronister A, et al: Genetic counseling for fragile X Syndrome: updated recommendations of the National Society of Genetic Counselors. J Genet Couns 2005;14(4):249-270

3. Sherman S, Pletcher BA, Driscoll DA: Fragile X syndrome: diagnostic and carrier testing (ACMG Practice Guideline). Genet Med 2005;7:584-587

Day(s) and Time(s) Performed

Monday, Wednesday; 10 a.m.

Analytic Time

4 days

CPT Code Information

81243-FMR1 (fragile 1 mental retardation 1) (eg, fragile X mental retardation) gene analysis; evaluation to detect abnormal (eg, expanded) alleles

Fibroblast Culture for Genetic Test

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

 

Amniotic Fluid Culture/Genetic Test

88235-Tissue culture for amniotic fluid (if appropriate)

88240-Cryopreservation (if appropriate)

 

Maternal Cell Contamination, B

81265-Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (eg, pre-transplant recipient and donor germline testing, post-transplant non-hematopoietic recipient germline [eg, buccal swab or other germline tissue sample] and donor testing, twin zygosity testing or maternal cell contamination of fetal cells (if appropriate)

 

81244-FMR1 (Fragile 1 mental retardation1) gene analysis, characterization of alleles (eg, expanded size and methylation status)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
FXS Fragile X Syndrome, Mol. Analysis In Process

 

Result ID Test Result Name Result LOINC Value
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 49549-9
52877 Released By No LOINC Needed

Test Classification

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 U.S. Food and Drug Administration.
Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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