Journal Article

Dysferlin is a Plasma Membrane Protein and is Expressed Early in Human Development

Louise V. B. Anderson, Keith Davison, Jennifer A. Moss, Carol Young, Michael J. Cullen, John Walsh, Margaret A. Johnson, Rumaisa Bashir, Stephen Britton, Sharon Keers, Zohar Argov, Ibrahim Mahjneh, Françoise Fougerousse, Jacques S. Beckmann and Kate M. D. Bushby

in Human Molecular Genetics

Volume 8, issue 5, pages 855-861
Published in print May 1999 | ISSN: 0964-6906
Published online May 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.5.855
Dysferlin is a Plasma Membrane Protein and is Expressed Early in Human Development

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Recently, a single gene, DYSF, has been identified which is mutated in patients with limb-girdle muscular dystrophy type 2B (LGMD2B) and with Miyoshi myopathy (MM). This is of interest because these diseases have been considered as two distinct clinical conditions since different muscle groups are the initial targets. Dysferlin, the protein product of the gene, is a novel molecule without homology to any known mammalian protein. We have now raised a monoclonal antibody to dysferlin and report on the expression of this new protein: immunolabelling with the antibody (designated NCL-hamlet) demonstrated a polypeptide of ∼230 kDa on western blots of skeletal muscle, with localization to the muscle fibre membrane by microscopy at both the light and electron microscopic level. A specific loss of dysferlin labelling was observed in patients with mutations in the LGMD2B/MM gene. Furthermore, patients with two different frame-shifting mutations demonstrated very low levels of immunoreactive protein in a manner reminiscent of the dystrophin expressed in many Duchenne patients. Analysis of human fetal tissue showed that dysferlin was expressed at the earliest stages of development examined, at Carnegie stage 15 or 16 (embryonic age 5–6 weeks). Dysferlin is present, therefore, at a time when the limbs start to show regional differentiation. Lack of dysferlin at this critical time may contribute to the pattern of muscle involvement that develops later, with the onset of a muscular dystrophy primarily affecting proximal or distal muscles.

Journal Article.  4848 words.  Illustrated.

Subjects: Genetics and Genomics

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