Rabbit Anti-Human APTX Polyclonal antibody

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia type 1 (AOA1) is caused by mutations in the gene encoding aprataxin (APTX). Although several in vitro findings proposed that impaired enzymatic activities of APTX are responsible for EACH/AOA1, potential instability of mutant proteins has also been suggested as the pathogenesis based on in vivo finding that mutant proteins are almost undetectable in EAOR/AOA1 tissues or cells. The present study aimed to experimentally prove instability of mutant proteins in neuronal cells, the cell type preferentially affected by this disease. Results of pulse-chase experiments demonstrated that all of the disease-associated mutants had extremely shorter half-lives than the WT. We further found that mutants were targeted for rapid proteasome-mediated degradation. These results help establish pathogenic and physiological protein characteristics of APTX in neuronal cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Background. Phenotype-genotype correlations, generally based on predominant associated signs, are being increasingly used to distinguish different types of autosomal recessive cerebellar ataxias (ARCA). Case reports. Two brothers developed signs of cerebellar ataxia with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. The examination also showed oculomotor apraxia. Sural nerve biopsy revealed conspicuous reduction in the density of myelinated fibres but preservation of unmyelinated nerve fibres. Blood tests revealed low serum albumin and elevated cholesterol. A homozygous W279X truncating mutation was identified in exon 6 of the APTX gene, confirming the diagnosis of cerebellar ataxia with oculomotor apraxia type 1 (AOA1). Conclusions. These cases illustrate the presentation of AOA1 type of ARCA and discuss the role of peripheral neuropathy in the differential diagnostic of the ARCAs variants.