Check out the August 2016, Volume #3, Issue #8 of our newsletter.
FXN (NM_000144.4) encodes the frataxin protein which is a nuclear-encoded mitochondrial iron chaperone involved in iron-sulfur biogenesis and heme biosynthesis. It appears to be a key activator of mitochondrial energy conversion and oxidative phosphorylation (Ristow et al. PNAS. (2000) 97:12239-12243). FXN is located at 9q21.11 and is composed of 5 coding exons. This gene is most commonly associated with Friedreich ataxia (FRDA). More than 90% of individuals with FRDA carry an abnormally expanded GAA repeat in intron1 of FXN in both alleles. The remaining individuals with FRDA are compound heterozygotes for an abnormally expanded GAA repeat in the disease-causing range in one allele and another intragenic pathogenic variant in the other allele. Hypertrophic cardiomyopathy (HCM) is a common feature of FRDA, and cardiac complications are the leading cause of death in patients with FRDA (Payne et al. J Child Neurol. (2012) 27:1179-1186). Cardiomyopathy presentation with subsequent onset of ataxia has been reported in the literature (Leonard et al. Arch Dis Child. (2001) 84:167–168).