title: Miyoshi myopathy patients with novel 5' splicing donor site mutations showed different dysferlin immunostaining at the sarcolemma.
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.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. mineki@m3.kufm.kagoshima-u.ac.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Saito
authors.forename: Itsuro
authors.initials: I
authors.lastname: Higuchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Mineki
authors.initials: M
authors.lastname: Saito
authors.forename: Keiko
authors.initials: K
authors.lastname: Hirata
authors.forename: Masahito
authors.initials: M
authors.lastname: Suehara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Osame
mesh_terms: D000293:Adolescent; D000328:Adult; D000073939:Dysferlin; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis* / Q000235:genetics* / Q000276:immunology; D009135:Muscular Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics*; D012508:Sarcolemma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D022821:RNA Splice Sites