Test #:

8380

Turnaround Time:

2-3 weeks

Specimen Requirements:

Specimens should be shipped at room temperature in a leak-proof, rigid container with overnight delivery. To discuss minimum acceptable specimens for neonatal patients or for sample types not listed, please contact Allele Diagnostics.

• Peripheral whole blood in EDTA: 2-3 mL²

CPT Codes:

81243 x1

Ordering Requirements:

• Pediatric Cytogenetics Test Requisition Form

Condition Description:

Fragile X syndrome is characterized in males by moderate intellectual disability, developmental delay, and variable behavioral issues, such as attention-deficit/hyperactivity disorder (ADHD) symptoms, and/or temper tantrums. Autism spectrum disorder is common in more than half of individuals with Fragile X syndrome. Males affected by Fragile X syndrome may have characteristic craniofacial features, including a long face, prominent forehead, and large protruding ears. Additional prepubertal features present in males with Fragile X may include hypotonia, joint laxity, pes planus, scoliosis, and sleep disorders. After puberty, males affected by Fragile X syndrome may present with macroorchidism, anxiety, irritable/aggressive behavior, and cardiac complications including mitral valve prolapse or aortic root dilation.

Individuals heterozygous for an FMR1 full mutation may have a variable clinical presentation due to X-inactivation. Intellectual disability in these patients is typically mild. Other clinical findings and behaviors seen in males with fragile X have also been seen, with milder presentation and lower frequency. Premutation carriers of Fragile X may also exhibit clinical features such as premature ovarian failure, tremor, or ataxia.

Fragile X syndrome is caused by the FMR1 gene on the X chromosome and is associated with a triplet (CGG) repeat expansion in the promoter of the FMR1 gene. CGG expansion leads to methylation and subsequent inactivation of the FMR1 gene.

Clinical Utility:

• Individuals with intellectual disability, developmental delay, or autism
• Females known to be a carrier of fragile X syndrome (obligate carriers)
• Individuals with a family history of undiagnosed intellectual disability

Genes (1):

FMR1

Test Description:

Triplet Repeat Primed PCR and Capillary Electrophoresis

In individuals with normal alleles, the number of triplet (CGG) repeats ranges from approximately 5-44. Individuals with approximately 55-200 CGG repeats are premutation carriers. The number of repeats in the premutation range is likely to expand in subsequent generations, particularly when passed through female meiosis. Individuals with fragile X syndrome have over 200 CGG repeats. Males with over 200 repeats are almost always affected. Mosaicism, the presence of two different sized repeats or extent of methylation, for pre- and full mutation alleles has been reported in some individuals with FMR1 full CGG expansions.

This test analyses the FMR1 gene for CGG repeat expansions. Only the targeted CGG repeat expansions will be detected; other types of variants will not be detected. The methodology for this test is triplet repeat primed PCR and capillary electrophoresis. Both normal CGG repeat tracts and expanded CGG repeat tracts are detected by PCR amplification. Follow-up testing may be considered if indicated based on the initial results of this test.

Detection:

Normal: ≤ 44 CGG repeats. Intermediate: 45-54 unmethylated CGG repeats. Premutation: 55-200 CGG repeats and methylation of expanded allele. Full Mutation: > 200 CGG repeats and methylation of expanded allele. Some expanded alleles may fail to be recognized with a level less than 3% of total DNA. Although rare, false positive or false negative results may occur. All results should be interpreted in context of clinical findings, relevant history, and other laboratory data.

References:

• GeneReviews