| ||Fragile X (FMR1) Mutation Screen
|0040011||Fragile X (FMR1) Diagnostic
#ExistInterpData>Background Information for Fragile X (FMR1) Screen:
Characteristics: Fragile X syndrome, the most common heritable form of mental retardation, is characterized by moderate mental retardation in males and mild mental retardation in females, behavioral phenotype, connective tissue anomalies, and physical findings. Older male premutation carriers may develop fragile X-associated tremor/ataxia syndrome (FXTAS) characterized by progressive cerebellar ataxia and intention tremor. Female premutation carriers may develop premature ovarian insufficiency (20 percent), or rarely, FXTAS.
Incidence of Disease: 1 in 4000 males and 1 in 8000 females.
Incidence of Premutation: 1 in 1000 males and 1 in 350 females.
Inheritance: X-linked dominant.
Penetrance: Reduced in females.
Cause: CGG expansions in the 5' untranslated region of FMR1 leading to hypermethylation of the gene and inhibition of FMR1 transcription.
Full mutation: >200 CGG repeats (methylated)
Premutation: 55-200 CGG repeats (unmethylated)
Intermediate: 45-54 CGG repeats (unmethylated)
Common: 5-44 CGG repeats (unmethylated)
Clinical Sensitivity & Specificity: 99 percent for pre and full mutation alleles.
Methodology: PCR followed by capillary electrophoresis.
Analytic Sensitivity & Specificity: 99 percent.
Limitations: Rare FMR1 mutations, unrelated to trinucleotide expansion may not be detected. Precise sizing of the CGG repeats is not provided. Intermediate alleles will not be reported.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
See Compliance Statement C: www.aruplab.com/CS
||If the screen suggests a pre or full mutation, then Fragile X (FMR1) Diagnostic will be added for analysis of sizing and methylation. Additional charges apply.
If reflexed, add 81244
||Inherited Mental Retardation (Fragile X (FMR1) Screen with Reflex to Fragile X (FMR1) Diagnostic)
, Martin-Bell Syndrome (Fragile X (FMR1) Screen with Reflex to Fragile X (FMR1) Diagnostic)