title: Novel diagnostic paradigms for Friedreich ataxia.
abstract: Friedreich ataxia is the most common inherited ataxia, with a wide phenotypic spectrum. It is generally caused by GAA expansions on both alleles of FXN, but a small percentage of patients are compound heterozygotes for a pathogenic expansion and a point mutation. Two recent diagnostic innovations are further characterizing individuals with the phenotype but without the classic genotypes. First, lateral-flow immunoassay is able to quantify the frataxin protein, thereby further characterizing these atypical individuals as likely affected or not affected, and providing some correlation to phenotype. It also holds promise as a biomarker for clinical trials in which the investigative agent increases frataxin. Second, gene dosage analysis and the identification of affected individuals with gene deletions introduce a novel genetic mechanism of disease. Both tests are now clinically available and suggest a new diagnostic paradigm for the disorder. Genetic counseling issues and future diagnostic testing approaches are considered as well.
authors: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors: Karlla W
authors: KW
authors: Brigatti
authors: Eric C
authors: EC
authors: Deutsch
authors: David R
authors: DR
authors: Lynch
authors: Jennifer M
authors: JM
authors: Farmer
mesh_terms: D005621:Friedreich Ataxia / Q000175:diagnosis* / Q000235:genetics*; D005817:Genetic Counseling; D006801:Humans; D007118:Immunoassay; D033862:Iron-Binding Proteins / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin