Test Code: 5413

Premature Ovarian Failure: FMR1 CGG Repeat Analysis
Test Code: 5413
Turnaround time: 2 weeks

CONDITION DESCRIPTION

FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related premature ovarian failure (POF). FMR1-related premature ovarian failure (POF) is the onset of ovarian dysfunction or menopause before the age of 40 years. Women who are carriers of FMR1 premutation range expansions are at increased risk for POF (estimated as high as 21%), though penetrance of POF is not complete. Recent reports indicate that women who carry a premutation size expansion may have a slight increased risk for developing fragile X-associated tremor/ataxia syndrome (FXTAS), a disorder that causes tremors, balance problems, difficulty walking, and memory difficulty.

The FMR1 gene is located on the X chromosome. FMR1-related disorders are associated with the presence of a triplet (CGG) repeat expansion in the promoter of FMR1 leading to methylation and subsequent inactivation of the FMR1 gene. The normal range of CGG repeats is approximately 5-44. Repeats in this range are considered stable when passed from parent to child. Repeats in the 45-54 range are considered intermediate (or grey-zone), for which the risk of expansion to a full mutation of 200 repeats or more when passed to children is low but not well defined at this time. Individuals with approximately 55-200 CGG repeats are premutation carriers. Females with expansions in this range are at risk for POF. The number of repeats in this range is unstable and may expand when passed to children. Individuals with fragile X have over 200 CGG repeats. Males with over 200 repeats are almost always affected, while females may be more mildly affected. Women who are carriers of a full size expansion are not at increased risk of POF. Mosaicism has also been reported in some individuals with FMR1 mutations, indicating the presence of two different repeat sizes or variation in the extent of methylation.

References:
1. GeneReviews: https://www.ncbi.nlm.nih.gov/books/NBK1384/

GENES
FMR1

INDICATIONS
Testing is indicated for:

• Adult females with premature ovarian failure.

METHODOLOGY
The DNA surrounding the CGG repeat in the FMR1 gene is amplified by PCR and the size of the repeat is determined by capillary electrophoresis.

DETECTION AND REFERENCE RANGE
Detection: All cases of premutation expansion mutations for FMR1 will be detected by this assay.

Reference Range: Normal for FMR1: < 44 CGG repeats, Intermediate: 45-55 CGG repeats, Premutation: 55-~200 repeats, Full mutation: >200 CGG repeats.

SPECIMEN REQUIREMENTS

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Isolated DNA
Specimen Requirements:
In microtainer: 60 ug.
Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.

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