Miyoshi myopathy patients with novel 5′ splicing donor site mutations showed different dysferlin immunostaining at the sarcolemma

Akiko Saito, Itsuro Higuchi, Masanori Nakagawa, Mineki Saito, Keiko Hirata, Masahito Suehara, Yoshihiro Yoshida, Toshiaki Takahashi, Masashi Aoki, Mitsuhiro Osame

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22 Citations (Scopus)

Abstract

We analyzed five clinically defined cases of Miyoshi myopathy both genetically and immunologically. Western blot of muscle specimens confirmed that all of these patients had dysferlin deficiency. Immunohistochemistry revealed that two of the five patients showed positive dysferlin immunostaining. Subsequent mutation analysis of the dysferlin gene in these two patients revealed that both had novel 5′ splicing donor site mutations. One patient with a homozygous G to C substitution at nucleotide 1036+1 exon 6 splicing donor site showed patchy sarcolemmal dysferlin immunostaining. The second patient with both a heterozygous G to A substitution at nucleotide 1310+1 exon 10 splicing donor site and a heterozygous C to G substitution at nucleotide 1939 (which induces Tyr 522 Stop of exon 18) showed both patchy sarcolemmal and diffuse cytoplasmic dysferlin immunostaining. In contrast to Becker muscular dystrophy, the clinical course and severity of dysferlin staining positive patients was not clearly different from negative patients. These results suggest that a splicing mutation of the dysferlin gene may have the potential to cause decreased dysferlin expression but may not be related to the milder clinical phenotype.

Original languageEnglish
Pages (from-to)615-620
Number of pages6
JournalActa neuropathologica
Volume104
Issue number6
DOIs
Publication statusPublished - 2002

Keywords

  • Dysferlin
  • Immunohistochemistry
  • Miyoshi myopathy
  • Splicing mutation
  • Western blot

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Saito, A., Higuchi, I., Nakagawa, M., Saito, M., Hirata, K., Suehara, M., Yoshida, Y., Takahashi, T., Aoki, M., & Osame, M. (2002). Miyoshi myopathy patients with novel 5′ splicing donor site mutations showed different dysferlin immunostaining at the sarcolemma. Acta neuropathologica, 104(6), 615-620. https://doi.org/10.1007/s00401-002-0593-x