Fragile X (FMR1) with Reflex to Methylation Analysis, Fetal

Background information for Fragile X (FMR1) with Reflex to Methylation Analysis, Fetal
Characteristics of Fragile X syndrome (FXS): Affected males have moderate intellectual disability, hyperactivity, perseverative speech, social anxiety, poor eye contact, hand flapping or biting, autism spectrum disorders and connective tissue anomalies in males. Females are usually less severely affected than males.
Characteristics of Fragile X Tremor Ataxia Syndrome (FXTAS): Onset of progressive ataxia and intention tremor typically after the fourth decade of life. Females also have a 21 percent risk for primary ovarian insufficiency. Incidence of FXS: 1 in 4,000 Caucasian males and 1 in 8,000 Caucasian females.
Inheritance: X-linked.
Penetrance of FXS: Complete in males; 50 percent in females.
Penetrance of FXTAS: 47 percent in males and 17 percent in females >50 years of age.
Cause: Expansion of the FMR1 gene CGG triplet repeat.
Full mutation: typically >200 CGG repeats (methylated).
Premutation: 55 to approx 200 CGG repeats (unmethylated).
Intermediate: 45-54 CGG repeats (unmethylated).
Normal: 5-44 CGG repeats (unmethylated).
Clinical Sensitivity: 99 percent.
Methodology: Triplet repeat-primed polymerase chain reaction (PCR) followed by size analysis using capillary electrophoresis. Methylation-specific PCR analysis is performed for CGG repeat lengths of 55 or greater to distinguish between premutation and full mutation alleles.
Analytic Sensitivity and Specificity: 99 percent; estimated precision of sizing for intermediate and premutation alleles is within 2-3 CGG repeats.
Limitations: Methylation patterns may not be fully established in early gestation; thus, diagnostic testing on chorionic villus samples is not recommended. Diagnostic errors can occur due to rare sequence variations. Rare FMR1 variants unrelated to trinucleotide expansion will not be detected. A specific CGG repeat size estimate is not provided for full mutation alleles. AGG trinucleotide interruptions within the FMR1 CGG repeat tract are not assessed.

For quality assurance purposes, ARUP Laboratories will confirm the above result at no charge following delivery. Order Confirmation of Fetal Testing and include a copy of the original fetal report (or the mother's name and date of birth) with the test submission. Please contact an ARUP genetic counselor at (800) 242-2787 extension 2141 prior to specimen submission.