Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy

M. Aoki, J. Liu, I. Richard, R. Bashir, S. Britton, S. M. Keers, J. Oeltjen, H. E V Brown, S. Marchand, N. Bourg, C. Beley, D. McKenna-Yasek, K. Arahata, S. Bohlega, E. Cupler, I. Illa, I. Majneh, R. J. Barohn, J. A. Urtizberea, M. FardeauA. Amato, C. Angelini, K. Bushby, J. S. Beckmann, R. H. Brown

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Objective: Mutations in the skeletal muscle gene dysferlin cause two autosomal recessive forms of muscular dystrophy: Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). The purpose of this study was to define the genomic organization of the dysferlin gene and conduct mutational screening and a survey of clinical features in 21 patients with defined molecular defects in the dysferlin gene. Methods: Genomic organization of the gene was determined by comparing the dysferlin cDNA and genomic sequence in P1-derived artificial chromosomes (PACs) containing the gene. Mutational screening entailed conformational analysis and sequencing of genomic DNA and cDNA. Clinical records of patients with defined dysferlin gene defects were reviewed retrospectively. Results: The dysferlin gene encompasses 55 exons spanning over 150 kb of genomic DNA. Mutational screening revealed nine novel mutations associated with MM. The range of onset in this patient group was narrow with a mean of 19.0 ± 3.9 years. Conclusion: This study confirms that the dysferlin gene is mutated in MM and LGMD2B and extends understanding of the timing of onset of the disease. Knowledge of the genomic organization of the gene will facilitate mutation detection and investigations of the molecular biologic properties of the dysferlin gene.

Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalNeurology
Volume57
Issue number2
Publication statusPublished - Jul 24 2001

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Mutation
Genes
P1 Bacteriophage Artificial Chromosomes
Complementary DNA
Miyoshi myopathy
Muscular Dystrophies
DNA Sequence Analysis
Exons
Skeletal Muscle
DNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Aoki, M., Liu, J., Richard, I., Bashir, R., Britton, S., Keers, S. M., ... Brown, R. H. (2001). Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy. Neurology, 57(2), 271-278.

Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy. / Aoki, M.; Liu, J.; Richard, I.; Bashir, R.; Britton, S.; Keers, S. M.; Oeltjen, J.; Brown, H. E V; Marchand, S.; Bourg, N.; Beley, C.; McKenna-Yasek, D.; Arahata, K.; Bohlega, S.; Cupler, E.; Illa, I.; Majneh, I.; Barohn, R. J.; Urtizberea, J. A.; Fardeau, M.; Amato, A.; Angelini, C.; Bushby, K.; Beckmann, J. S.; Brown, R. H.

In: Neurology, Vol. 57, No. 2, 24.07.2001, p. 271-278.

Research output: Contribution to journalArticle

Aoki, M, Liu, J, Richard, I, Bashir, R, Britton, S, Keers, SM, Oeltjen, J, Brown, HEV, Marchand, S, Bourg, N, Beley, C, McKenna-Yasek, D, Arahata, K, Bohlega, S, Cupler, E, Illa, I, Majneh, I, Barohn, RJ, Urtizberea, JA, Fardeau, M, Amato, A, Angelini, C, Bushby, K, Beckmann, JS & Brown, RH 2001, 'Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy', Neurology, vol. 57, no. 2, pp. 271-278.
Aoki M, Liu J, Richard I, Bashir R, Britton S, Keers SM et al. Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy. Neurology. 2001 Jul 24;57(2):271-278.
Aoki, M. ; Liu, J. ; Richard, I. ; Bashir, R. ; Britton, S. ; Keers, S. M. ; Oeltjen, J. ; Brown, H. E V ; Marchand, S. ; Bourg, N. ; Beley, C. ; McKenna-Yasek, D. ; Arahata, K. ; Bohlega, S. ; Cupler, E. ; Illa, I. ; Majneh, I. ; Barohn, R. J. ; Urtizberea, J. A. ; Fardeau, M. ; Amato, A. ; Angelini, C. ; Bushby, K. ; Beckmann, J. S. ; Brown, R. H. / Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy. In: Neurology. 2001 ; Vol. 57, No. 2. pp. 271-278.
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AU - Aoki, M.

AU - Liu, J.

AU - Richard, I.

AU - Bashir, R.

AU - Britton, S.

AU - Keers, S. M.

AU - Oeltjen, J.

AU - Brown, H. E V

AU - Marchand, S.

AU - Bourg, N.

AU - Beley, C.

AU - McKenna-Yasek, D.

AU - Arahata, K.

AU - Bohlega, S.

AU - Cupler, E.

AU - Illa, I.

AU - Majneh, I.

AU - Barohn, R. J.

AU - Urtizberea, J. A.

AU - Fardeau, M.

AU - Amato, A.

AU - Angelini, C.

AU - Bushby, K.

AU - Beckmann, J. S.

AU - Brown, R. H.

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N2 - Objective: Mutations in the skeletal muscle gene dysferlin cause two autosomal recessive forms of muscular dystrophy: Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). The purpose of this study was to define the genomic organization of the dysferlin gene and conduct mutational screening and a survey of clinical features in 21 patients with defined molecular defects in the dysferlin gene. Methods: Genomic organization of the gene was determined by comparing the dysferlin cDNA and genomic sequence in P1-derived artificial chromosomes (PACs) containing the gene. Mutational screening entailed conformational analysis and sequencing of genomic DNA and cDNA. Clinical records of patients with defined dysferlin gene defects were reviewed retrospectively. Results: The dysferlin gene encompasses 55 exons spanning over 150 kb of genomic DNA. Mutational screening revealed nine novel mutations associated with MM. The range of onset in this patient group was narrow with a mean of 19.0 ± 3.9 years. Conclusion: This study confirms that the dysferlin gene is mutated in MM and LGMD2B and extends understanding of the timing of onset of the disease. Knowledge of the genomic organization of the gene will facilitate mutation detection and investigations of the molecular biologic properties of the dysferlin gene.

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