FRIEDREICH ATAXIA
DNA ANALYSIS
Also see: 6365 - Friedreich Ataxia (FRDA) - FXN Sequencing

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with an incidence of approximately 1 in 50,000. FRDA is characterized by progressive gait and limb ataxia, lack of tendon reflexes in the legs, loss of position sense, dysarthria, and pyramidal weakness of the legs. Hypertrophic cardiomyopathy is found in almost all patients and diabetes mellitus is seen in 10% of the patients. The age of onset is usually around puberty, almost always before 25 years with a slow progression of the disease. A molecular analysis is available for a complex differential diagnosis suggesting FRDA. The mutation responsible for FRDA resides in a novel gene (X25) which maps to 9q13 and is characterized by expansion of an unstable GAA trinucleotide repeat. In approximately 95% of cases normal individuals have 7-34 repeats, while FRDA patients have expansions of 66 repeats or greater. To date, alleles between the normal and abnormal ranges have not been observed. Due to limitations in test methodology, alleles 35 to 60 repeats may not be distinguished from those under 35 repeats. Correlations of length of the repeat with age of onset of disease are not precise enough to be used clinically.

Reasons for Referral:

Confirmation of diagnosis of individuals with mental retardation or developmental delay.
Carrier or predictive testing for asymptomatic individuals with a positive family history for FRDA. Molecular analysis of the affected relative or both of the carrier parents is recommended.

We recommend that genetic and/or psychological counseling be made available to all individuals considering having confirmatory, carrier or predictive testing for FRDA.

Testing Methodology:

Direct Mutation Analysis: Long PCR analysis across the GAA region of the X25 gene to determine allele sizes. All normal sized alleles and the vast majority of expanded alleles will be detected in this analysis. Southern analysis is used to identify extremely large GAA repeat expansions and to confirm the PCR results. Allele sizes will be reported as approximations and size ranges are subject to change as more information becomes available.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adults: 14 cc; Child: 6 cc; Infant: 2-3 cc
Requisition form must accompany specimen. Prior to any genetic testing, we recommend genetic counseling and request that the subject, or a legal guardian, sign our consent form and submit it with the sample.

Turnaround Time:

3 weeks

CPT Codes and Prices:

83898x2, 83891, 83912, 83892x2, 83894x3, 83896, 83897

Shipping Information

Forms:

>> DNA Requisition

Test Code:

6031