2,543 research outputs found
Genetic analysis of limb girdle muscular dystrophy and Miyoshi myopathy
No full textThe autosomal recessive muscular dystrophies encompass limb girdle muscular dystrophy (LGMD) and Miyoshi myopathy (MM), which can show clinical and genetic overlap. In this study we have made good progress towards understanding the molecular basis of LGMD2I and non-dysferlin MM. Our work on LGMD2I involved haplotype analysis of chromosome 19ql3.3 to identify potential LGMD2I families. We generated a primary transcript map of the LGMD2I region. During this work, mutations in FKRP were described in LGMD2I and MDCIC. In 3 of our families showing potential linkage to 19ql3.3, FKRP mutations were identified. A common mutation in FKRP, C826A (Leu276Ile), is associated with LGMD2I and this mutation was present in 2 of our families and in >70% of the LGMD2I families studied. Genotype-phenotype correlations show this mutation is associated with a milder disease course. FKRP is a predicted glycosyhransferase and mutations in its gene appear to be a common cause of muscular dystrophy. Our work on the analysis of non-dysferlin MM supports the existence of a MM gene, designated MMD2, on chromosome lOp. We have defined a 25Mb region on chromosome 10 shared by affecteds in 2 non-dysferlin MM families. In 5 further families, additional haplotype analysis is required to confirm exclusion from chromosome l0p.In the non-dysferlin MM families haplotype analysis of the caveolin 3 region on chromosome 3 has suggested no involvement of caveolin 3 in non-dysferlin MM. SSCP analysis and sequencing has failed to identify mutation in caveolin 3. The confirmation of the MMD2 gene and identification of recombinant boundaries, allowing candidate gene analysis, will allow us to identify the MMD2 gene
Studies on muscular dystrophy associated genes
No full textMuscular dystrophy is a collective group of genetic disorder that results in progressive wasting of skeletal muscle. Dysferlin, the gene responsible for Limb Girdle Muscular Dystrophy type 2B (LGMD2B) and Miyoshi Myopathy (MM) was found to be a member of a newly identified protein family named the ferlins. Recent work has suggested that dysferlin is necessary for efficient calcium sensitive membrane resealing therefore is involved in membrane repair, a mechanism which if defective results in progressive muscle wasting. In this project, the involvement of other genes that could possibly be associated with muscular dystrophy is investigated. Myoferlin, a member of the ferlin protein family is highly homologous to dysferlin and is also a plasma membrane protein with six C2 domains and a C-terminus transmembrane domain. To date no disease has been associated with mutations in the myoferlin gene but its high similarity to dysferlin means that it could be a potential muscular dystrophy associated gene. Results obtained from this study strongly suggest that myoferlin like dysferlin is enriched at plasma membrane disruption sites and during myoblast differentiation, two processes which involve the fusion of two opposed bilayers, a process vital in membrane repair. In addition, a fifth member of the ferlin protein family is reported in this project and the primary results obtained are consistent with it being a potential muscular dystrophy associated gene. Finally, a group of MM affected families that were previously excluded for mutations in their dysferlin gene were analysed for muscular dystrophy associated genes other than dysferlin
Miyoshi-type distal muscular dystrophy - Clinical spectrum in 24 Dutch patients
No full textMiyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history, muscle CT-scans and muscle biopsy findings. Our study shows that Miyoshi myopathy is a heterogeneous, slowly progressive disorder. The disease starts with weakness and atrophy of the calves and progressively involves the proximal leg and hip muscles and, in a later stage the shoulder and upper arm muscles. After 10 years disease duration, one-third of the patients are dependent on wheelchairs for out-of-door transportation. Disease progression is related to disease duration and not to early age of onset of symptoms. Onset may be at any age and is asymmetrical in roughly half of the cases. Four cases had been initially diagnosed as idiopathic hyper-CK-aemia.</p
Letter from Beverly Toyama and Hideki Obayashi to Miyoshi, January 2010
No full textA letter from Beverly Toyama and Hideki Obayashi to Miyoshi-san, informing him of the Kurata Ranch Reunion, which will take place in Gardena, California. The letter provides instructions regarding the time and location of the event, as well as suggested items for attendees to bring with them. It also includes a copy of a hand drawn map of Kurata Ranch, which is based on the recollection of Ume Murata.The James H. Osborne Nisei Collection contains mainly correspondence between Emiko and Usami Terada, incarcerees in the Rohwer incarceration camp, McGehee Arkansas, and the Thomas family in Lawndale, California, and photographs of the Teradas and the Thomases. The letters describe the trip from the Santa Anita Temporary Assembly Center to the Rohwer incarceration camp, their lives and conditions in the camp, and their concerns about their properties in Lawndale, California. Also included are photographs taken in the camp, some issues of "The Rohwer outpost," and fliers published during wartime
Miyoshi-type distal muscular dystrophy. Clinical spectrum in 24 Dutch patients
No full textMiyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history muscle CT-scans and muscle biopsy findings. Our study shows that Miyoshi myopathy is a heterogeneous, slowly progressive disorder. The disease starts with weakness and atrophy of the calves and progressively involves the proximal leg and hip muscles and in a later stage the shoulder and upper arm muscles. After 10 years disease duration, one-third of the patients are dependent on wheelchairs for out-of-door transportation. Disease progression is related to disease duration and not to early age of onset of symptoms. Onset may be at any age and is asymmetrical in roughly half of the cases. Four cases had been initially diagnosed as idiopathic hyper-CK-aemia
Vivaldi's Four Seasons and the Globalization of Musical Taste
No full text"Vivaldi's Four Seasons, or at least parts of it, can be recognised by enormous numbers of people on this planet, and its sounds seem to come from almost every elevator shaft, mobile phone, restaurant and television advert in the world. It stands as the very epitome of a globalized artwork, and therefore it would be reasonable to suppose that globalization theories would be a great help in explaining its success. That this may not be the case is one of the main points of this paper -�� but before we get to that, there are two matters that have to be set in place. The first is to define the characteristics of the Four Seasons as a global commodity (note that I refer to it in the singular, since the four individual pieces come as a package); the second is to describe the main tenets of globalization theories and some of their chief generating ideas. Trying to map the characteristics of the work onto the assertions of the theories will be the main business of this paper, and this process is designed not only to illuminate the work, but also to test the theories." (Excerpt, introduction
Identification of a Dysferlin Gene Mutation in a Korean Case with Miyoshi Myopathy
No full textRecent genetic and immunohistochemical analyses have shown that Miyoshi myopathy (MM) is caused by a mutation in the DYSF gene, which induces dysfunction of dysferlin. The author described one patient showing characteristic MM phenotype with deficiency of dysferlin on immunohistochemistry. Direct DNA sequencing of whole exons of DYSF gene revealed one homozygous missense mutation (G1165C) on exon 12, which let to an amino acid substitution from the glutamic acid to glutamine at the 389 of the peptide sequence in this patient. This is the first reported case of MM confirmed by immunohistochemical and genetic analyses in Korea.ope
Holocence envirommental changes in the Choshi Peninsula and its surroundings,eastern Kanto, central Japan(2)
No full textSolution structure of the inner DysF domain of myoferlin and implications for limb girdle muscular dystrophy type 2b
No full textMutations in the protein dysferlin, a member of the ferlin family, lead to limb girdle muscular dystrophy type 2B and Myoshi myopathy. The ferlins are large proteins characterised by multiple C2 domains and a single C-terminal membrane-spanning helix. However, there is sequence conservation in some of the ferlin family in regions outside the C2 domains. In one annotation of the domain structure of these proteins, an unusual internal duplication event has been noted where a putative domain is inserted in between the N- and C-terminal parts of a homologous domain. This domain is known as the DysF domain. Here, we present the solution structure of the inner DysF domain of the dysferlin paralogue myoferlin, which has a unique fold held together by stacking of arginine and tryptophans, mutations that lead to clinical disease in dysferlin
Crystal structures of the human Dysferlin inner DysF domain
No full textBackground: Mutations in dysferlin, the first protein linked with the cell membrane repair mechanism, causes a group of muscular dystrophies called dysferlinopathies. Dysferlin is a type two-anchored membrane protein, with a single C terminal trans-membrane helix, and most of the protein lying in cytoplasm. Dysferlin contains several C2 domains and two DysF domains which are nested one inside the other. Many pathogenic point mutations fall in the DysF domain region.
Results: We describe the crystal structure of the human dysferlin inner DysF domain with a resolution of 1.9 Angstroms. Most of the pathogenic mutations are part of aromatic/arginine stacks that hold the domain in a folded conformation. The high resolution of the structure show that these interactions are a mixture of parallel ring/guanadinium stacking, perpendicular H bond stacking and aliphatic chain packing.
Conclusions: The high resolution structure of the Dysferlin DysF domain gives a template on which to interpret in detail the pathogenic mutations that lead to disease
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