%0 Journal Article
%T Is Friedreich ataxia an epigenetic disorder?
%A Daman Kumari
%A Karen Usdin
%J Clinical Epigenetics
%D 2012
%I BioMed Central
%R 10.1186/1868-7083-4-2
%X Friedreich ataxia (FRDA) (OMIM 229300; http://www.omim.org/entry/229300 webcite), first described in 1863 by Nikolaus Friedreich, is a relentlessly progressive disorder caused by mutations in the frataxin (FXN) gene. It is the most common heritable ataxia in Caucasians [1]. The major pathological changes include loss of myelinated axons in peripheral neurons, particularly in the dorsal root ganglia, the degeneration of posterior columns of the spinal cord and the loss of peripheral sensory nerve fibers. Myocardial muscle fibers also degenerate and are replaced by macrophages and fibroblasts. The net result of these and other changes include not only limb and gait abnormalities, but also hypertrophic cardiomyopathy, limb muscle weakness, absent lower limb reflexes and a positive extensor plantar response (Babinski sign). Decreased vibration sense, skeletal abnormalities, dysarthria, and diabetes are common comorbid features. Many symptoms become apparent during adolescence. Loss of ambulation occurs roughly 15 years after disease onset with > 95% of patients becoming wheelchair bound by the age of 45. Early mortality due primarily to cardiac failure is not uncommon [2,3].FRDA is inherited in an autosomal recessive fashion. The affected gene, frataxin (FXN) (OMIM 606829; http://omim.org/entry/606829 webcite), is located on chromosome 9q13 in humans [4]. The first intron contains a GAA£¿TTC repeat tract embedded in the central poly(A) tract of an AluSq element from which it probably arose [5]. The GAA£¿TTC repeat tract, which is located approximately 1.3 kb downstream of the major FXN transcription start site (TSS), is polymorphic in the human population (Figure 1). While normal alleles have between 8 to 33 repeats, most individuals with FRDA have 2 FXN alleles each with > 90 repeats, the majority having 600 to 900 repeats [4]. A minority of patients (approximately 4%) are compound heterozygotes, having one allele with > 90 repeats and a second allele with a small deleti
%K Friedreich ataxia
%K heterochromatin
%K histone modifications
%K transcription
%K splicing
%K triplex
%U http://www.clinicalepigeneticsjournal.com/content/4/1/2