Mutational analysis in dysferlin gene in patients with muscular dystrophy in Japanese populations.

日本人群肌营养不良症患者 Dysferlin 基因突变分析。

• 批准号: 12557058
• 负责人: ITOYAMA Yasuto
• 金额: $ 8.45万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557058/
• 关键词: autosomal recessive; dysferlin; limb girdle type muscular dystrophy; Miyoshi myopathy; muscular dystrophy; mutation

MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the gene dysferlin. This gene is also mutated in families with limb girdle muscular dystrophy (LGMD) 2B. To study dysferlin gene mutations in Japanese patients with Miyoshi myopathy (MM) and undertake genotype-phenotype correlations in this disease, we examined 57 Japanese families with MM or LGMD. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism (SSCP) or direct sequencing from the PCR fragments. We identified mutations in 34 families with MM patients and 24 families with LGMD. Mutations in Japanese patients are distributed along the entire length of the gene. Five mutations (G1310+1A, C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 59 percent of the mutations in this study. We speculated that most patients with MM were selectively affected in the paravertebral muscles even in the very early stage. This study revealed that the G3370T and G3510A mutations are respectively associated with the mild and more severe forms of MM.

MM 是一种常染色体隐性遗传性远端肌营养不良症，由 Dysferlin 基因突变引起。该基因在肢带型肌营养不良症 (LGMD) 2B 家族中也发生突变。为了研究日本三好肌病 (MM) 患者的 Dysferlin 基因突变并研究该疾病的基因型-表型相关性，我们检查了 57 个患有 MM 或 LGMD 的日本家庭。从患者的外周淋巴细胞中提取基因组DNA。通过单链构象多态性（SSCP）或从PCR片段直接测序来筛选55个外显子中每一个的PCR产物。我们在 34 个 MM 患者家庭和 24 个 LGMD 家庭中发现了突变。日本患者的突变分布在基因的整个长度上。 5 个突变（G1310+1A、C1939G、G3370T、3746delG 和 4870delT）在该人群中相对更为普遍，占本研究中突变的 59%。我们推测，大多数多发性骨髓瘤患者即使在早期阶段也会选择性地受到椎旁肌肉的影响。这项研究表明，G3370T 和 G3510A 突变分别与轻度和更严重的 MM 相关。

项目成果

Tateyama M, Aoki M, Nishino I, Hayashi YK, Sekiguchi S, Shiga Y, Takahashi T, Onodera Y, Haginoya K, Kobayashi K, Iinuma K, Nonaka I, Arahata K, Itoyama Y: "Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy"Neurology. 58. 323-325 (

Tateyama M、Aoki M、Nishino I、Hayashi YK、Sekiguchi S、Shiga Y、Takahashi T、Onodera Y、Haginoya K、Kobayashi K、Iinuma K、Nonaka I、Arahata K、Itoyama Y：“caveolin-3 基因突变

Aoki M et al.: "Genomic organization and novel mutations in dysferlin gene in Miyoshi myopathy and limb girdle dystrophy type 2B"Neurology. 57. 271-278 (2001)

Aoki M 等人：“三好肌病和 2B 型肢带营养不良中 Dysferlin 基因的基因组组织和新突变”神经病学。

Aoki M et al.: "Cenomic organization and novel mutations in dysferlin gene in Miyoshi myopathy and limb girdle dystrophy type 2B"Neurology. 57. 271-278 (2001)

Aoki M 等人：“Miyoshi 肌病和肢带营养不良 2B 型中的细胞组织和 Dysferlin 基因的新突变”神经病学。

Aoki M, Liu J, Richard I, Keers SM, Marchand S, Bourg N, McKenna-Yasek D, Arahata K, Bushby K, Beckmann J, Brown RH Jr.: "Genomic organization and novel mutations in dysferlin gene in Miyoshi myopathy and limb girdle dystrophy type 2B"Neurology. 57. 271-2

Aoki M、Liu J、Richard I、Keers SM、Marchand S、Bourg N、McKenna-Yasek D、Arahata K、Bushby K、Beckmann J、Brown RH Jr.：“三好肌病和 Dysferlin 基因的基因组组织和新突变

Matsuda C, Hayashi YK, Ogawa M, Aoki M, Murayama K, Nishino I, Nonaka I, Arahata K, Brown RH Jr.: "The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle"Hum Mol Genet. 10. 1761-1766 (2001)

Matsuda C、Hayashi YK、Okawa M、Aoki M、Murayama K、Nishino I、Nonaka I、Arahata K、Brown RH Jr.：“肌膜蛋白 Dysferlin 和 Caveolin-3 在骨骼肌中相互作用”Hum Mol Genet。