眼球運動失行と低アルブミン血症を伴う早発型脊髄小脳失調症

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia（EAOH/AOA1）

眼球運動失行と低アルブミン血症を伴う早発型脊髄小脳失調症（EAOH/AOA1）は，本邦における常染色体遺伝性脊髄小脳変性症の中で約半数を占める疾患である。臨床症状の特徴は，病初期に眼球運動失行がみられ，失調性言語，失調性歩行などの小脳症状が緩徐に進行し，やがて末梢神経障害，低アルブミン血症，高コレステロール血症を示すようになる。原因遺伝子aprataxin（APTX）の同定後，核質，核小体への局在，一本鎖DNA修復関連蛋白であるXRCC1との蛋白相互作用，および核酸に対する加水分解作用が示され，一本鎖DNA損傷修復に関連した生理機能が推定されている。

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ataxia-oculomotor apraxia 1（EAOH/AOA1）is an autosomal recessive ataxia clinically characterized by early-onset progressive ataxia, ocular motor apraxia, peripheral neuropathy and hypoalbuminemia. Aprataxin（APTX）was identified as a causative gene for EAOH/AOA1 in 2001. APTX shows nuclear and nucleolar localization by western blot analysis of subcellular fractionations and immunocytochemistry. The C-terminus of APTX has a histidine-triad（HIT）motif, which is predicted to bind the nucleotides and functions as a nucleotidyl hydrolase. The N-turminus of APTX has a folk-head-associated（FHA）domain which interacts with the X-ray repair cross-complementing group 1（XRCC1）, the scaffold protein in the single strand break repair（SSBR）machinery. Lymphoblastoid cells of EAOH/AOA1 patients show high sensitivity to H₂O₂ and alkylating agents that break the DNA strand The physiological function of APTX is speculated to play a role in the process of SSBR.