J Korean Med Sci.  2006 Aug;21(4):724-727. 10.3346/jkms.2006.21.4.724.

Clinical and Genetic Analysis of Korean Patients with Miyoshi Myopathy: Identification of Three Novel Mutations in the DYSF Gene

• Cho HJ
• Sung DH
• Kim EJ
• Yoon CH
• Ki CS
• Kim JW

• KMID: 2157828
• DOI: http://doi.org/10.3346/jkms.2006.21.4.724

Abstract

Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy caused by mutations in the dysferlin gene (DYSF) on chromosome 2p13. Although MM patients and their mutations in the DYSF gene have been found from all over the world, there is only one report of genetically confirmed case of MM in Korea. Recently, we encountered three unrelated Korean patients with MM and two of them have previously been considered as having a type of inflammatory myopathy. The clinical and laboratory evaluation showed typical features of muscle involvement in MM in all patients but one patient initially had moderate proximal muscle involvement and another showed incomplete quadriparesis with rapid progression. Direct sequencing analysis of the DYSF gene revealed that each patient had compound heterozygous mutations (Gln832X and Trp992Arg, Gln832X and Trp999Cys, and Lys1103X and Ile1401HisfsX8, respectively) among which three were novel. Although MM has been thought to be quite rare in Korea, it should be considered in a differential diagnosis of patients exhibiting distal myopathy.

Keyword

Distal Myopathies; Muscular Diseases; DYSF protein, human; Muscular Dystrophies, Limb-Gir-dle; Mutation

MeSH Terms

Mutation, Missense/genetics
Mutation/*genetics
Muscular Dystrophies/*genetics/pathology
Muscle Proteins/*genetics
Membrane Proteins/*genetics
Male
Korea
Humans
Genes, Recessive/genetics
Female
DNA Mutational Analysis
Codon, Nonsense/genetics
Base Sequence
Amino Acid Sequence
Adult

Figure

• 

  Fig. 1 Novel DYSF gene mutations identified in the present study (arrows). (A) A nonsense mutation (c.2494C>T; Gln832X) observed in patients 1 and 2; (B) a missense mutation (c.2974T>C; Trp992Arg) observed in patient 2; and (C) a nonsense mutation (c.3307A>T; Lys1103X) observed in patient 3.

Reference

1. Miyoshi K, Kawai H, Iwasa M, Kusaka K, Nishino H. Autosomal recessive distal muscular dystrophy as a new type of progressive muscular dystrophy. Seventeen cases in eight families including an autopsied case. Brain. 1986. 109:31–54.

2. Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, Serrano C, Urtizberea JA, Hentati F, Hamida MB, Bohlega S, Culper EJ, Amato AA, Bossie K, Oeltjen J, Bejaoui K, McKenna-Yasek D, Hosler BA, Schurr E, Arahata K, de Jong PJ, Brown RH Jr. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet. 1998. 20:31–36.

3. Bashir R, Britton S, Strachan T, Keers S, Vafiadaki E, Lako M, Richard I, Marchand S, Bourg N, Argov Z, Sadeh M, Mahjneh I, Marconi G, Passos-Bueno MR, Moreira Ede S, Zatz M, Beckmann JS, Bushby K. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet. 1998. 20:37–42.

4. Illa I, Serrano-Munuera C, Gallardo E, Lasa A, Rojas-Garcia R, Palmer J, Gallano P, Baiget M, Matsuda C, Brown RH. Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. Ann Neurol. 2001. 49:130–134.

5. Hong SC, Kim BJ, Lee EA, Suh YL. Distal myopathy of Miyoshi type: 1 case. J Korean Neurol Assoc. 1999. 17:916–919.

6. Jeon SH, Jang H, Lee CH, Kim HC, Kim JH. Miyoshi myopathy: a case report. J Korean Acad Rehabil Med. 1999. 23:425–429.

7. Lee YH, Park KJ, Lee KS, Lee L, Kim DS, Choi NC, Kwon OY, Lim BH. A case of Miyoshi type distal myopathy. J Korean Neurol Assoc. 2001. 19:555–557.

8. Oh SH, Kim TS, Choi YC. Identification of a dysferlin gene mutation in a Korean case with Miyoshi myopathy. Yonsei Med J. 2004. 45:927–930.

9. Takahashi T, Aoki M, Tateyama M, Kondo E, Mizuno T, Onodera Y, Takano R, Kawai H, Kamakura K, Mochizuki H, Shizuka-Ikeda M, Nakagawa M, Yoshida Y, Akanuma J, Hoshino K, Saito H, Nishizawa M, Kato S, Saito K, Miyachi T, Yamashita H, Kawai M, Matsumura T, Kuzuhara S, Ibi T, Sahashi K, Nakai H, Kohnosu T, Nonaka I, Arahata K, Brown RH Jr, Saito H, Itoyama Y. Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype. Neurology. 2003. 60:1799–1804.

10. Harihara S, Saitou N, Hirai M, Gojobori T, Park KS, Misawa S, Ellepola SB, Ishida T, Omoto K. Mitochondrial DNA polymorphism among five Asian populations. Am J Hum Genet. 1988. 43:134–143.

11. Park MH, Kim HS, Kang SJ. HLA-A,-B,-DRB1 allele and haplotype frequencies in 510 Koreans. Tissue Antigens. 1999. 53:386–390.

12. Gallardo E, Rojas-Garcia R, de Luna N, Pou A, Brown RH Jr, Illa I. Inflammation in dysferlin myopathy: immunohistochemical characterization of 13 patients. Neurology. 2001. 57:2136–2138.

13. McNally EM, Ly CT, Rosenmann H, Mitrani Rosenbaum S, Jiang W, Anderson LV, Soffer D, Argov Z. Splicing mutation in dysferlin produces limb-girdle muscular dystrophy with inflammation. Am J Med Genet. 2000. 91:305–312.