Fragile X Syndrome DNA Testing
- Fragile X Syndrome DNA Testing
- Start Date
- Expiration Date
- CPT Codes
- 83890; 83892; 83894; 83896; 83897; 83898; 83909; 83912
- Reference Test
Lavender, EDTA Whole Blood
Preferred specimen volume: 14 ml
Adult: 7.0-14.0 mL
Pediatric: 3.0 mL
- Transport Info
- Fasting Required?
- Patient Instructions
- Reference Range
Polymerase Chain Reaction (PCR)
FMR1 molecular genetic testing should be offered in individuals with mental retardation, developmental delay, or autism, especially if they have family history of Fragile X syndrome or relatives with undiagnosed mental retardation.
Individuals seeking reproductive counseling who have a family history of Fragile X syndrome or of undiagnosed mental retardation should be offered FMR1 molecular genetic testing.
Mothers who are carriers should be offered prenatal testing by amniotic fluid testing.
FMR1 testing is helpful in confirming the diagnosis of Fragile X syndrome when the initial diagnosis was made by cytogenetic testing or when cytogenetic testing is ambiguous or discordant with the clinical features of the individual.
Fragile-X syndrome is the most common cause of inherited mental retardation, seen in approximately 1/1200 males and 1/2500 females. Patients with this syndrome exhibit mental retardation and characteristic physical features and behavior. Testing should be considered in any individual with unexplained mental retardation or with a family history of mental retardation that is consistent with an X-linked pattern of inheritance. Testing is beneficial for confirmation of a clinical diagnosis, presymptomatic evaluation of individuals who are at-risk, and prenatal diagnosis of at-risk pregnancies. Fragile-X positive patients have an expanded three letter codon (CGG) abnormality repeated within the fragile-X gene. Normally, X chromosomes have 5-50 repeats of this triplet; fragile-X positive chromosomes exhibit hundreds to thousands of repeats. (Similar triplet expansions cause myotonic dystrophy, Huntington disease, and Kennedy disease.) Expansion of the repeat in excess of 200 copies typically results in a FMR-1 gene that is non-functional. Traditionally, testing for fragile-X syndrome has involved cytogenetic analysis of peripheral blood samples from individuals suspected of having the congenital disorder. This testing includes routine-banded chromosome studies, as well as examination of cells grown in medium, which allows for expression of the X chromosome fragile site. Novel molecular-based assays have recently been developed that are more sensitive and potentially more accurate for fragile-X analysis (96% detection rate). PCR can be used to produce millions of copies of the small region of DNA from the X chromosome that contains the fragile-X repeat. Specificity is achieved by directing the reaction using two complementary primers on either side of the region of interest. Once amplified, the size of the product can be measured to detect the number of triplets present and, hence, whether the mutation is present. Therefore, the combination of standard cytogenetic analysis and molecular testing appears to be the optimal approach to define this entity in the laboratory setting. The advantages of ARUP's complementary approach to fragile-X analysis include:
Elimination of time consuming/less sensitive chromosomal fragile site studies
Increased sensitivity of fragile-X detection
Continued detection of additional chromosomal abnormalities
Identification of the premutation state, frequently seen in carriers of fragile-X
Mosaic males who have a normal or premutation allele and a full expansion.
Due to the unique nature of genetic testing, patients should receive pre-test and post-test counseling. Informed consent is recommended.
Normal: Alleles range from 5 to 44 repeats and are stably transmitted without any increase or decrease in repeat number.
Intermediate: Alleles range from ~45 to ~54. Females with occasional minor increases or decreases in repeat number usually transmit these stably.
Premutation: Alleles range from ~55 to ~ 200 repeats and are not associated with mental retardation. Women with alleles in this range are at risk for having affected children. Males with an allele in this range produce daughters who are at risk for having affected children.
Full Mutation: Has over 200 repeats with several hundred to several thousand repeats being typical. Abnormal hypermethylation of the deoxycytidylate residues contained in the CGG repeats usually occurs once CGG repeats exceed ~200.