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

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

Authors

M Aoki

J Liu

I Richard

R Bashir

S Britton

SM Keers

J Oeltjen

HEV Brown

S Marchand

N Bourg

C Beley

D McKenna-Yasek

K Arahata

S Bohlega

E Cupler

I Illa

I Majneh

RJ Barohn

JA Urtizberea

M Fardeau

A Amato

C Angelini

K Bushby

JS Beckmann

RH Brown



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.

Citation

Aoki, M., Liu, J., Richard, I., Bashir, R., Britton, S., Keers, S., …Brown, R. (2001). Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy. Neurology, 57(2), 271-278. https://doi.org/10.1212/wnl.57.2.271

Journal Article Type Article
Publication Date Jul 1, 2001
Deposit Date May 18, 2007
Journal Neurology
Print ISSN 0028-3878
Electronic ISSN 1526-632X
Publisher Lippincott, Williams & Wilkins
Peer Reviewed Not Peer Reviewed
Volume 57
Issue 2
Pages 271-278
DOI https://doi.org/10.1212/wnl.57.2.271
Keywords Girdle muscular-dystrophy, Fertilization-defective mutants, Caenorhabditis-elegans, Chromosome 2P, SJL mice, Locus, 2B, Modifier, Protein, Sperm.
Publisher URL http://www.neurology.org/cgi/content/abstract/57/2/271