Identity of hereditary cerebellar ataxia, peripheral neuropathy, and hypoalbuminemia

遗传性小脑共济失调、周围神经病和低蛋白血症的鉴别

• 批准号: 13670821
• 负责人: TACHI Nobutada
• 金额: $ 1.98万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670821/
• 关键词: EOCA-HA; AOA; Aprataxin gene; FLJ20157; AOA1 gene

Early onset cerebellar ataxia with hypoalbuminemia (EOCA-HA) in Japan and autosomal recessive trait of cerebellar ataxia with ocular aparaxia (AOA) in Portugal are clinically and genetically allelelic disorders. Candidate gene of those disorders are located at chromosome 9pl3.3 by homozygous mapping. Its candidate gene was called "Aprataxin". The human aparataxin gene was about 10 kb length and its cDNA was 2.2kb length with 7 exons. The long transcript was constituted with 342 amino acids and the short form was constiyuted with 168 by alternative splicing in exon 3. The mutation of aprataxin gene in EOCA-HA showed most of 689 insertion T homozygously, and small number of compound heterozygote of 689 insertion T and 617C-T. Present our 5 cases had all 689 insertion T homozygously. Based on those observations, 689 insertion T was founder in Japanese EOCA-HA patients.

日本的早发性小脑性共济失调伴低蛋白血症（EOCA-HA）和葡萄牙的常染色体隐性遗传的小脑性共济失调伴眼失用（AOA）都是临床和遗传等位基因疾病。通过纯合作图，这些疾病的候选基因位于染色体9pl3.3。其候选基因被称为“Aprataxin”。人aparataxin基因长约10kb，其cDNA长度为2.2kb，有7个外显子。长转录本由342个氨基酸组成，短转录本由168个氨基酸组成，通过外显子3的选择性剪接构成。EOCA-HA中aprataxin基因的突变显示大部分689插入T纯合，少数689插入复合杂合子T 和 617C-T。目前我们的5个病例全部689个插入T都是纯合的。根据这些观察结果，689 插入 T 是在日本 EOCA-HA 患者中形成的。

项目成果

Tachi N, Kozuka N, Chiba S et al.: "A dopuble mutation in a patient with X-linked myotubular myoapthy"Pediatr Neurol. 24. 297-299 (2001)

Tachi N、Kozuka N、Chiba S 等人：“X 连锁肌小管肌病患者的双重突变”Pediatr Neurol。

Tachi N, Chiba S, Matsuo M: "Fukuyama type congenital muscular dystrophy associated with a lack of C-terminal domain of dystrophin"Pediatric Neurol. 24. 373-378 (2001)

Tachi N、Chiba S、Matsuo M：“福山型先天性肌营养不良症与肌营养不良蛋白 C 末端结构域缺乏相关”Pediatric Neurol。

Moreira MC, Barbot C, Tachi N, Kozuka N, Mendonca P, Barros J, Coutinho P, Sequeiros J, Koenig M: "Homozygosity mapping of Portuguese and Japanese forms of ataxia-oculomotor apraxia to 9pl3, and evidence for genetic heterogeneity"Am J Hum Genet. 68. 501-5

Moreira MC、Barbot C、Tachi N、Kozuka N、Mendonca P、Barros J、Coutinho P、Sequeiros J、Koenig M：“葡萄牙和日本形式的共济失调-动眼神经失用症与 9pl3 的纯合性映射，以及遗传异质性的证据”Am

Moreira MC, Barbot C, Tachi N et al.: "Homozygosity mapping of Portuguese and Japanese forms of ataxia-oculomotor apraxia to 9p13, and evidence for genetic heterogeneity"Am J Hum Genet. 68. 501-508 (2001)

Moreira MC、Barbot C、Tachi N 等人：“葡萄牙和日本形式的共济失调-动眼神经失用症到 9p13 的纯合性映射，以及遗传异质性的证据”Am J Hum Genet。

Tachi N, Kozuka N, Chiba S, Miyaji M, Watanabe I: "A double mutation in a patient with x-linked myotubular myopathy"Pediatr Neurol. 24. 297-299 (2001)

Tachi N、Kozuka N、Chiba S、Miyaji M、Watanabe I：“x 连锁肌管肌病患者的双重突变”Pediatr Neurol。