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 mL
Fragile X syndrome is characterized by moderate intellectual disability, particularly in males. It has a prevalence of 1/4000 to 1/6000 in the general population, and is a leading genetic cause of intellectual disability. Males with fragile X syndrome may have a recognizable facial pattern with a long face, protruding ears, and a large head. Some males with fragile X have joint laxity. After puberty, males develop macroorchidism. Boys may have characteristic behaviors that vary with age: young children may have autistic-like features, hyperactivity or tantrums. Older children may have poor eye contact, shyness, and attention problems.
Females with fragile X may have a variable clinical presentation due to X-inactivation. Intellectual disability in females is typically mild. Other clinical findings and behaviors seen in males with fragile X have also been seen in females, with milder presentation and lower frequency.
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. In individuals with normal alleles, the number of 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.
- 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
Performed using PCR amplification
Both normal CGG repeat tracts and expanded CGG repeat tracts are detected by PCR amplification. Methylation studies may be added upon provider request if the result does not fit the patient's phenotype.
Normal: Approximately 5-44 CGG repeats. Intermediate: Approximately 45-54 unmethylated CGG repeats. Premutation: Approximately 55-200 CGG repeats and methylation of expanded allele. Affected: Over 200 CGG repeats and methylation of expanded allele.