Fragile X Syndrome, DNA Analysis, Prenatal
| Fragile X Syndrome, DNA Analysis, Prenatal | | | |
| Number | | 510073 |
| CPT | | 83891; 83900; 83909; 83912; 88235 |
| Related Information | | Fragile X Syndrome, DNA Analysis |
| Synonyms | | Martin-Bell Syndrome |
| Special Instructions | | Pertinent medical findings. Include name, age, gender of
fetus (if known), and affected relatives (if any).
Chorionic villus samples (CVS) are not acceptable for this
DNA analysis. Note: Call 800-345-GENE with questions. |
| Specimen | | Amniotic fluid (Note: Chorionic villus samples (CVS) are not acceptable for fragile X prenatal testing.) |
| Volume | | 10 mL |
| Minimum Volume | | 5 mL |
| Container | | Sterile plastic conical tube or two confluent T25 flasks |
| Storage Instructions | | Maintain specimen at room temperature. |
| Causes for Rejection | | Frozen specimen; chorionic villus specimens are not acceptable |
| Use | | Identify carrier and/or affected individuals with fragile X. Recommended without cytogenetics when an affected individual has already been identified within the family. Counseling is available for positive cases. |
| Methodology | | Polymerase chain reaction (PCR) followed by agarose gel and capillary electrophoresis, and if required, Southern blot hybridization |
| Additional Information | | Fragile X syndrome (OMIM 309550) is the most common known form of inherited mental retardation, affecting 16-25 of 100,000 males. Prevalence among females is approximately half what is reported for males. In almost every case, the disorder arises from an expansion of a CGG repeat polymorphism in the 5′ untranslated region of the FMR1 gene. The expansion commonly occurs in the maternal line of transmission. The normal repeat range is defined as 54 repeats and smaller. Patients with 55 to 200 CGG repeats are regarded as premutation carriers. Premutations are unstable and prone to further expansion in the next generation, such that females with premutations are at high risk of having a child with a full mutation (>200 repeats). The high end of the normal range (45-54 repeats) is considered a gray zone. Gray zone carriers are unlikely to have children with full mutations, but subsequent generations may be at risk. The full mutation is associated with methylation of the FMR1 promoter region that abrogates gene expression and elicits the fragile X phenotype of mental retardation/developmental delay, commonly with characteristic facial and gonadal features. Premutation carriers will not exhibit the features. Females may experience premature ovarian failure (POF), while men (and, less commonly, women) over age 50 years may exhibit an ataxia and tremor phenotype (FXTAS) with similarities to parkinsonism. This test is appropriate not only for pregnancies with a known family history of fragile X syndrome, but for other unexplained familial mental retardation as well. It is a highly accurate means of identifying fragile X syndrome. |
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