Fragile X CGG repeat analysis for buccal specimens1

Test #:

8381

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.

CPT Codes:

81243 x1

Ordering Requirements:
Condition Description:

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.

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:

Performed using PCR amplification, methylation-sensitive PCR, and Southern blot.

Both normal CGG repeat tracts and expanded CGG repeat tracts are detected by PCR amplification, using a CGG repeat-specific probe, and capillary electrophoresis. Expanded CGG repeat tracts will be reflexed to a gene specific PCR and sized by agarose gel electrophoresis. DNA methylation analysis will be performed on any full expansions detected, Methylation sensitive PCR for Males and Southern blot for females.

Detection:

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.

References:
  • GeneReviews
Footnotes:
  1. This test is performed at a partner lab of Allele Diagnostics.
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