Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S, Koike R, Hiroi T, Yuasa T, Awaya Y, Sakai T, Takahashi T, Nagatomo H, Sekijima Y, Kawachi I, Takiyama Y, Nishizawa M, Fukuhara N, Saito K, Sugano S, Tsuji S
Department of Neurology, Brain Research Institute, Niigata University, 1 Asahimachi, Niigata 951, Japan.
Nat Genet. 2001 Oct;29(2):184-8. doi: 10.1038/ng1001-184.
Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.
弗里德赖希共济失调（FRDA）是欧洲人和欧洲裔人群中最常见的常染色体隐性神经退行性疾病，其特征为发病早（通常在25岁之前）、进行性共济失调、感觉丧失、腱反射消失以及腿部锥体束征性肌无力。我们最近发现了一组独特的患者，他们的临床表现具有常染色体隐性遗传、发病年龄早、类似FRDA的临床表现以及低白蛋白血症的特点。然而，与FRDA基因座的连锁关系被排除。鉴于这些临床表现与最近描述的与9号染色体p13区相关的动眼性失用共济失调（AOA）的临床表现相似，我们证实我们患者的疾病也与同一基因座相关。我们缩小了候选区域，并确定了一个编码组氨酸三联体（HIT）超家族成员的新基因作为“致病”基因。我们将其产物命名为aprataxin；基因符号为APTX。尽管已经鉴定出许多HIT蛋白，但aprataxin是第一个与独特表型相关的蛋白。
