LabPLUS is part of Auckland District Health Board
and provides medical laboratory testing
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| MOLECULAR GENETICS TESTS - FRAGILE X SYNDROME |
| Background: Fragile X syndrome is an X-linked disorder with variable expression in carrier males and females. Approximately 1 in 1100 males and 1 in 700 females carry the gene for this condition. Affected males typically have a long face with prominent jaw, protruding ears, large head, large testicles and can have joint hyperextensibility and mitral valve prolapse. They usually have moderate to severe mental retardation, behaviour problems including autistic behaviour, speech and language delays. Of males who carry the gene, 20% are clinically normal. Carrier females can show physical signs of the condition, and 35% of carriers are mentally retarded to varying degrees although usually to a milder degree than affected males. Many show emotional difficulties, problem solving difficulties and learning disabilities. While the gene responsible for the Fragile X syndrome is on the X chromosome, it has unusual inheritance characteristics. In general, these characteristics can be explained by the nature of the mutation within the fragile X gene (FMR-1). The normal gene contains a three base pair sequence (referred to as a CGG repeat) which is repeated a given number of times on each X chromosome, typically between 5 and 50 times. Although variable in the general population, the number of repeats is usually inherited without change from generation to generation. The principle mutation causing Fragile X syndrome is an amplification of the CGG repeat sequence. Small increases in the number of these repeats (most often in the range of 50 - 200) are called premutations and are not typically associated with phenotypic effects in females or males (the latter are often called "transmitting males"). Transmission of a premutation by males to their daughters usually results in further amplification, either to a larger premutation or to a "full mutation," which can be several hundred to thousands of repeats long. The full mutation is also associated with abnormal methylation of a region adjacent to the FMR-1 gene. This is thought to interfere with normal FMR-1 gene expression, resulting in the Fragile X phenotype in males and in some carrier females. A few individuals diagnosed clinically with Fragile X syndrome do not have the amplification-type mutation. These individuals may have a different type of mutation within the FMR-1 gene (e.g. deletion or point mutation) or a mutation in another gene. Although the exact frequency is unknown, it is likely that less than 5% of affected individuals fall into this amplification-negative category. However, because of this possibility, the most accurate results will be obtained when an affected individual or obligate carrier is tested to verify the type of mutation in a family before testing at risk family members. This molecular test, which identifies the CGG repeat amplification in FMR-1, does not rule out other genetic causes of mental subnormality, such as chromosome anomalies. Among patients with non-specific mental retardation, 3.7% have full mutation of the FMR-1 gene and thus Fragile X syndrome, and 3.6% have chromosome abnormalities other than Fragile X. Unless there is a documented history of Fragile X syndrome in the patient's family, both molecular and conventional cytogenetic studies for other chromosome anomalies are indicated. Analysis:
Blood: 3 x 4.0mL whole blood into EDTA tubes . Invert several times to mix. Forward within 24-48 hours at ambient temperature. Paediatric Samples: Minimum of 3mL whole blood in EDTA tubes. Prenatal Samples:
6 weeks once sample is received. Cost of test: FX - $676.11 Note: Prices excludes GST (12.5%) and may change without notice. Please click on a link below to view information about another specific test.
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