| A B C D E F G H I J K L M N O P Q R S T U V W X Y Z # |
FRAGILE X, PCR REFLEX SOUTHERN
Test Code510234
Alias/See Also
FRAXA
CPT Codes
81243
Preferred Specimen
"Whole blood
10 mL"
10 mL"
Transport Container
"Lavender-top (EDTA) tube or yellow-top (ACD) tube
"
"
Transport Temperature
room temp
Specimen Stability
room temperature
Reject Criteria (Eg, hemolysis? Lipemia? Thaw/Other?)
"Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container
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"
Methodology
"Polymerase chain reaction (PCR) followed by capillary electrophoresis, and, if required, Southern blot hybridization "
Clinical Significance
"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.
Fragile X syndrome (OMIM 309550) is the most common known form of inherited mental retardation, affecting 16 to 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 fewer. 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 primary ovarian insufficiency (POI), while men (and, less commonly, women) older than 50 may exhibit an ataxia and tremor phenotype (FXTAS) with similarities to parkinsonism."
Fragile X syndrome (OMIM 309550) is the most common known form of inherited mental retardation, affecting 16 to 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 fewer. 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 primary ovarian insufficiency (POI), while men (and, less commonly, women) older than 50 may exhibit an ataxia and tremor phenotype (FXTAS) with similarities to parkinsonism."
