Chromosome High Resolution and Fragile X
Chromosome High Resolution and Fragile X | | | |
| Number | | 510115 |
| CPT | | 83891; 83900; 83909; 83912; 88230; 88262; 88289; 88291 |
| Synonyms | | Chromosome Analysis, High Resolution and Fragile X DNA ; Cytogenetics, High Resolution and Fragile X DNA ; Inherited Mental Retardation ; Martin-Bell Syndrome |
| Test Includes | | Direct molecular (DNA) analysis for fragile X plus complete high resolution chromosome analysis |
| Special Instructions | | Include name, age, gender, and relevant clinical history. For prenatal testing, please contact Genetics Services at 800-533-4353. |
| Specimen | | Whole blood |
| Volume | | 10 mL in lavender-top (EDTA) tube or yellow-top (ACD) tube and 10 mL in green-top (heparin) tube |
| Minimum Volume | | 7 mL in lavender-top (EDTA) or yellow-top (ACD) tube and 2 mL in green-top (heparin) tube. Note: Molecular genetic testing for fragile X syndrome may require Southern blot analysis, which requires relatively large amounts of DNA. Low volume blood collections may not be sufficient to complete testing in these cases. |
| Container | | Lavender-top (EDTA) tube or yellow-top (ACD) tube and green-top (heparin) tube |
| Storage Instructions | | Maintain specimen at room temperature. |
| Causes for Rejection | | Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container |
| Use | | This test is appropriate not only for cases with a known family history of fragile X syndrome, but for any case of unexplained mental retardation as well. It is an accurate means of identifying fragile X syndrome or other chromosomally-caused retardation syndromes. Fragile X premutation testing is also appropriate for some investigations of female infertility (POF) and parkinsonism. |
| Methodology | | Polymerase chain reaction (PCR) followed by agarose gel and capillary electrophoresis, and, if required, Southern blot hybridization; cytogenetic studies |
| 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. |
| References | | Hagerman PJ and Hagerman RJ, “The Fragile X Premutation: A Maturing Perspective,” Am J Hum Genet, 2004, 74(5):805-16. Jacquemont S, Hagerman RJ, Lechey MA, et al, “Penetrance of the Fragile X-Associated Tremor/Ataxia Syndrome in Premutation Carrier Population,” JAMA, 2004, 291(4):460-9. Maddalena A, Richards CS, McGinnis MJ. et al, “Technical Standards and Guidelines for Fragile X: The First of a Series of Disease-Specific Supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics,” Quality Assurance Subcommittee of the Laboratory Practice Committee, Genet Med, 2001; 3(3):200-5. Park V, Howard-Peebles P, Sherman S, et al, “Policy Statement: American College of Medical Genetics Fragile X Syndrome: Diagnostic and Carrier Testing,” Am J Med, 1994, 53(4):380-1. |
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