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

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12557058
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: ITOYAMA Yasuto Tohoku University School of Medicine, Department of Neurology, Professor, 大学院・医学系研究科, 教授 (30136428)
• Co-Investigator(Kenkyū-buntansha): AOKI Masashi Tohoku University School of Medicine, Department of Neurology, Research Associate, 医学部・附属病院, 助手 (70302148)
• Project Period (FY): 2000 – 2001
• Keywords: autosomal recessive / dysferlin / limb girdle type muscular dystrophy / Miyoshi myopathy / muscular dystrophy / mutation

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Matsuda C et al.: "The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle"Human Mol Genet. 10. 1761-1766 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tateyama M et al.: "Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy"Neurology. 58. 323-325 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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. 271-278 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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 (2002)
  • Description: 「研究成果報告書概要(欧文)」より