FRIEDREICH ATAXIA (FRDA)
FXN Sequencing
DNA ANALYSIS
Also see: 6031 - Friedreich Ataxia (FRDA) - GAA expansion mutation testing

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 and weakness, loss of position sense, and dysarthria. 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. The mutations responsible for FRDA reside in the frataxin gene (FXN) which maps to chromosome 9q13. While approximately 96% of individuals with FRDA have a homozygous GAA trinucleotide repeat expansion in intron 1 of the FXN gene, approximately 4% of patients are compound heterozygotes for a disease-causing expansion on one allele and have an inactivating FXN mutation on the other allele that may be detectable by DNA sequencing.

Reasons for Referral:

Confirmation of a clinical diagnosis for symptomatic individuals who have had a GAA expansion previously identified on one allele. For more information, please see GAA expansion mutation testing.
Carrier or predictive testing for asymptomatic individuals with a positive family history for a FXN point mutation (molecular analysis of the affected relative or both of the carrier parents is recommended)
We recommend that genetic counseling be made available to all individuals considering having confirmatory, carrier or predictive testing for FRDA.

Testing Methodology:

Full Sequencing: There are two isoforms of the FXN gene, which differ at exons 4 and 5 . PCR amplification of the 5 exons of the FXN coding region of both isoforms will be performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Analytical Sensitivity:

~99%

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adults: 14 cc; Child: 6 cc; Infant: 2-3 cc

Turnaround Time:

4 weeks

CPT Codes and Prices:

Index: 83891, 83898, 83894, 83904, 83909, 83912
Known Familial Mutation: 83891, 83898, 83894, 83904x2, 83909x2, 83912

Shipping Information

Forms:

>> Gene Sequencing Requisition
>> DNA Requisition

References:

1. Gellera C et al. Frataxin gene point mutations in Italian Friedreich ataxia patients. Neurogenetics, 2007 Nov;8(4):289-99. Epub 2007 Aug 17.
2. OMIM: #229300

Test Code:

Index: 6365
Known Familial Mutation: 6366