Research and treatment of hereditary neuropathy

遗传性神经病的研究和治疗

• 批准号: 18591141
• 负责人: HAYASAKA Kiyoshi
• 金额: $ 2.57万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591141/
• 关键词: Charcot-Marie-Tooth disease; hereditary neuropath; DHPLC; MLPA; CMT1A; 髄鞘; 遺伝子欠失; 抹消神経; MLPA; PRX; Nav1.6

Charcot-Marie-Tooth disease (CMT) is a most common hereditary neuropathy and is a genetically heterogeneous disease. Many responsible genes have been identified, however, disease-causing mutations had not been identified in many Japanese patients. So we established denaturing high performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) methods for screening of major disease-causing genes. We studied many Japanese patients with no CMT1A duplication and detected 15 cases with MPZ mutations, 18 cases with GJB1 mutations, 6 cases with PMP22, 1 case with EGR2 mutations and 4 cases with PRX mutations in demyelinating CMT using DHPLC method. As for axonal CMT, DHPLC screening detected 3 cases with MPZ mutations, 2 cases with GJB1 mutations and 10 cases with MFN2 mutations. In addition, DHPLC screening detected 2 cases with HSP27 mutations in distal hereditary motor neuropathy. MLPA screening did not detect a change in gene copy numbers except for CMT1A (PMP22) duplication. Nine cases were found to have CMT1A duplications and 3 of them had not been found by Southern blot hybridization or FISH methods. Our study confirmed that a change in gene copy numbers except for PMP22 is not a cause of CMT and MLPA is more sensitive to detect CMT1A duplication than Southern blot hybridization or FISH methods.

腓骨肌萎缩症（CMT）是一种最常见的遗传性神经病，是一种遗传异质性疾病。许多相关基因已被确定，然而，在许多日本患者中尚未确定致病突变。因此，我们建立了变性高效液相色谱（DHPLC）和多重连接依赖探针扩增（MLPA）方法用于筛选主要致病基因。我们研究了许多没有CMT1A重复的日本患者，并使用DHPLC方法检测了15例MPZ突变，18例GJB 1突变，6例PMP 22突变，1例EGFR 2突变和4例PRX突变的脱髓鞘CMT。DHPLC筛查轴突型CMT中MPZ突变3例，GJB1突变2例，MFN 2突变10例。此外，DHPLC筛查发现2例远端遗传性运动神经病HSP27突变。MLPA筛查未检测到除CMT1A（PMP 22）重复外的基因拷贝数变化。9例有CMT1A重复，其中3例Southern杂交或FISH均未发现。我们的研究证实，除了PMP22基因拷贝数的变化不是CMT的原因，MLPA比Southern印迹杂交或FISH方法更敏感地检测CMT1A重复。

项目成果

Charoot-Marie-Tooth病の遺伝子診断

Charoot-Marie-Tooth 病的基因诊断

• 发表时间: 2007
• 作者: Kotani T;Sutomo R;Sasongko TH;Sadewa AH;Gunadi;Minato T;Fujii E;Endo S;Lee MJ;Ayaki H;Harada Y;Matsuo M;Nishio H.;阿部暁子・木島一己・早坂 清
• 通讯作者: 阿部暁子・木島一己・早坂 清

A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome)

• DOI: 10.1086/518903
• 发表时间: 2007-08-01
• 期刊: AMERICAN JOURNAL OF HUMAN GENETICS
• 影响因子: 9.8
• 作者: Kato, Mitsuhiro;Saitoh, Shinji;Hayasaka, Kiyoshi
• 通讯作者: Hayasaka, Kiyoshi

Abstract Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease.

摘要 日本腓骨肌萎缩症患者的 Periaxin 突变。

• 发表时间: 2006
• 期刊: J Hum Genet. 51(7)
• 作者: Otagiri T;他
• 通讯作者: 他

Charcot-Marie-Tooth病の遺伝子診断

腓骨肌萎缩症的基因诊断

• 发表时间: 2007
• 作者: 阿部暁子;木島一己;早坂 清
• 通讯作者: 早坂 清

A longer polyalanine expansion in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattem (Ohtahara syndrome)

ARX 基因中较长的聚丙氨酸扩增导致早期婴儿癫痫性脑病，伴有抑制爆发型（大田原综合征）

• 发表时间: 2007
• 期刊: Am J Hum Genet 81
• 作者: Kato;M・Saitoh;S・Kamei;A・Shiraishi;H・Ueda;Y・Akasaka;M・Tohyama;J・Akasaka;N・Hayasaka;K
• 通讯作者: K