Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene
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DOI：
10.1038/ng1001-184
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发表时间：
2001-10-01
期刊：
影响因子：
30.8
通讯作者：
Tsuji, S
中科院分区：
文献类型：
--
作者：
Date, H;Onodera, O;Tsuji, S
Friedreich 共济失调 (FRDA) 是欧洲人和欧洲血统人群中最常见的常染色体隐性神经退行性疾病，其特点是发病早（通常在 25 岁之前）、进行性共济失调、感觉丧失、腱反射缺失和腿部锥体肌无力 (1-4)。我们最近发现了一组独特的患者，其临床表现以常染色体隐性遗传、发病年龄早、FRDA 样临床表现和低白蛋白血症为特征。然而，与 FRDA 位点的连锁被排除。鉴于临床表现与最近描述的与染色体 9p13 相关的共济失调伴动眼神经失用症 (AOA) 的相似性，我们证实我们患者的疾病也与相同的基因座有关 (5)。我们缩小了候选区域的范围，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。我们将其产品称为aprataxin；基因符号是APTX。尽管许多 HIT 蛋白已被鉴定，但 aprataxin 是第一个与独特表型相关的蛋白。
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(1-4). 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(5). 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.