Fragile X syndrome is the most common known cause of inherited mental retardation. The absence or deficit of the FMR1 protein (FMRP) is the fundamental defect in fragile X syndrome. In most cases, this results from presence of a full mutation (>200 CGG repeats) in the fragile X (FMR1) gene. Full mutations are associated with methylation and subsequent silencing of the FMR1 gene. In a few cases, the mutation involved is a deletion or point mutation in the FMR1 gene.
FMRP is important for normal brain development. Studies indicate that FMRP is involved in the translation of other proteins and may play a role in synaptic maturation. Males with a fully methylated full mutation have severely reduced or absent FMRP expression. Mosaic males (full mutation and either a premutation or a normal-sized allele) and males with a partially methylated full mutation may have intermediate expression of FMRP. For these categories of males, studies indicate that the presence of FMRP in greater than 50% of lymphocytes tends to be associated with a milder phenotype. In females with a full mutation, expression of FMRP is widely variable.
Determination of FMRP expression in mosaic males or males with a partially methylated full mutation provides prognostic information in some cases. For males who fit the clinical profile of fragile X syndrome but lack a CGG expansion, substantially decreased FMRP expression supports the diagnosis. This protein analysis is particularly useful in cases involving FMR1 deletions. FMRP expression is an additional piece of information that can be utilized by clinicians in caring for individuals with fragile X syndrome.
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- Indications for Testing:
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Males who have had fragile X DNA testing with any of the following results:
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Absence of a CGG repeat mutation in the FMR1 gene but clinical presentation consistent with fragile X syndrome
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Full mutation, partially methylated |
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Mosaic (full mutation plus premutation) |
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Mosaic (full mutation plus normal-sized allele) |
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Deletion or point mutation in the FMR1 gene or promoter region
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FMRP testing is not indicated for females |
Methodology:
| Immunocytochemistry test using an antibody specific for FMRP. FMRP expression is reported as the percent of lymphocytes positive for FMRP. |
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Our Fragile X Protein (FMRP) Test Service Provides:
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Detailed reports with genetic interpretation, recommendations, and education |
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Genetic consultation by board-certified genetic counselors and geneticists
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Specimen Requirements:
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3 ml whole blood in a lavender top tube (EDTA) received no more than 24 hours after draw
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Turnaround Time:
Please call Kimball Genetics for more information.
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