Molecular genetic analysis of dysferlin in Japanese patients with Miyoshi myopathy

Matsumura, Tsuyoshi; Akiyama, Masashi; Nagano, Atsushi J.; Hayashi, Yukiko; Asada, Chie; Ogawa, Megumu; Yamanaka, Gaku; Goto, Kanako; Nakagawa, Masanori; Oka, Hisayoshi; Sahashi, Ko; Kouhara, Nobuo; Saito, Yuko; Brown, Robert H.; Nonaka, Ikuya; Arahata, Kiichi

doi:10.2183/pjab.75.207

Cited by 13 publications

(15 citation statements)

References 6 publications

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“…Although six of the mutations (C1939G, G3016ϩ1A, G3370T, 3746delG, 5122-5123delCAϩA5121T, and 6071-6072delAG) were previously reported in MM or LGMD pedigrees, 9,11,18,19 10 of the mutations (G1036ϩ1C, C1064T, G1310ϩ1A, C2131A, G4376T, 4870delT, G5093T, G5409A, 6048delT, and 6159insGATC) are novel. For each putative mutation, we tested 100 normal chromosomes to determine whether the candidate change represented a common polymorphism by SSCP or restriction analysis.…”

Section: Methodsmentioning

confidence: 96%

“…Twenty-eight patients were included in review of the clinical profiles: 20 patients with dysferlin mutations in this study and 8 Japanese patients identified in previous studies 11,18 (additional information available at the Neurology Web site). Twenty-eight patients were included in review of the clinical profiles: 20 patients with dysferlin mutations in this study and 8 Japanese patients identified in previous studies 11,18 (additional information available at the Neurology Web site).…”

Section: Methodsmentioning

confidence: 99%

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Dysferlin mutations in Japanese Miyoshi myopathy

Takahashi

Akiyama²,

Tateyama³

et al. 2003

Neurology

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Section: Methodsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Dysferlin mutations in Japanese Miyoshi myopathy

Takahashi

Akiyama²,

Tateyama³

et al. 2003

Neurology

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“…Two mutations lie within the DysfNC domain, a nested repeat sequence in many ferlins and several other proteins, whose function is unknown. Missense mutations within this domain in dysferlin have been linked to Miyoshi myopathy (Aoki et al, 2001;Matsumura et al, 1999) also indicating its importance.…”

Section: +mentioning

confidence: 99%

FER-1 regulates Ca2+-mediated membrane fusion during C. elegans spermatogenesis

Washington

Ward

2006

Journal of Cell Science

129

148

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FER-1 is required for fusion of specialized vesicles, called membranous organelles, with the sperm plasma membrane during Caenorhabditis elegans spermiogenesis. To investigate its role in membranous organelle fusion, we examined ten fer-1 mutations and found that they all cause the same defect in membrane fusion. FER-1 and the ferlin protein family are membrane proteins with four to seven C2 domains. These domains commonly mediate Ca2+-dependent lipid-processing events. Most of the fer-1 mutations fall within these C2 domains, showing that they have distinct, non-redundant functions. We found that membranous organelle fusion requires intracellular Ca2+ and that C2 domain mutations alter Ca2+ sensitivity. This suggests that the C2 domains are involved in Ca2+ sensing and further supports their independent function. Using two immunological approaches we found three FER-1 isoforms, two of which might arise from FER-1 by proteolysis. By both light and electron microscopy, these FER-1 proteins were found to be localized to membranous organelle membranes. Dysferlin, a human homologue of FER-1 involved in muscular dystrophy, is required for vesicle fusion during Ca2+-induced muscle membrane repair. Our results suggest that the ferlin family members share a conserved mechanism to regulate cell-type-specific membrane fusion.

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“…Therefore, the final diagnosis of dysferlinopathy requires identification of mutations in the dysferlin gene. We first reported dysferlin mutations in Japanese patients with MM 10 and in a patient from a non-European ethnic group with distal anterior compartment myopathy (DACM), 11 a relatively new phenotype of dysferlinopathy. 12 Furthermore, we revealed that, in MM, four mutations (c.1566C>G, c.2997G>T, c.3373delG and c.4497delT) were relatively more prevalent in the Japanese population and the c.2997G>T mutation was associated with late onset.…”

Section: Introductionmentioning

confidence: 99%

Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B

Takahashi

Akiyama

Suzuki

et al. 2012

Journal of Neurology, Neurosurgery & Psychiatry

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Objective and methodsDysferlin encoded by DYSF deficiency leads to two main phenotypes, limb girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy. To reveal in detail the mutational and clinical features of LGMD2B in Japan, we observed 40 Japanese patients in 36 families with LGMD2B in whom dysferlin mutations were confirmed.Results and conclusionsThree mutations (c.1566C>G, c.2997G>T and c.4497delT) were relatively more prevalent. The c.2997G>T mutation was associated with late onset, proximal dominant forms of dysferlinopathy, a high probability that muscle weakness started in an upper limb and lower serum creatine kinase (CK) levels. The clinical features of LGMD2B are as follows: (1) onset in the late teens or early adulthood, except patients homozygous for the c.2997G>T mutation; (2) lower limb weakness at onset; (3) distal change of lower limbs on muscle CT at an early stage; (4) impairment of lumbar erector spinal muscles on muscle CT at an early stage; (5) predominant involvement of proximal upper limbs; (6) preservation of function of the hands at late stage; (7) preservation of strength in neck muscles at late stage; (8) lack of facial weakness or dysphagia; (9) avoidance of scoliosis; (10) hyper-Ckaemia; (11) preservation of cardiac function; and (12) a tendency for respiratory function to decline with disease duration. It is important that the late onset phenotype is found with prevalent mutations.

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Molecular genetic analysis of dysferlin in Japanese patients with Miyoshi myopathy

Cited by 13 publications

References 6 publications

Dysferlin mutations in Japanese Miyoshi myopathy

Dysferlin mutations in Japanese Miyoshi myopathy

FER-1 regulates Ca2+-mediated membrane fusion during C. elegans spermatogenesis

Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B

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