• Title, Summary, Keyword: LGMD

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Limb-girdle Muscular Dystrophy (지대형 근이양증)

  • Kim, Dae-Seong
    • Annals of Clinical Neurophysiology
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    • v.6 no.2
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    • pp.65-74
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    • 2004
  • Limb-girdle muscular dystrophy (LGMD) is a heterogeneous group of inherited muscle disorders caused by the mutations of different genes encoding muscle proteins. In the past, when the molecular diagnostic techniques were not available, the subtypes of muscular dystrophies were classified by the pattern of muscle weakness and the mode of inheritance, and LGMD had been considered as a 'waste basket' of muscular dystrophy because many unrelated heterogeneous cases with 'limb-girdle' weakness were put into the category of LGMD. With the advent of molecular genetics at the end of the last century, it has been known that there are many subtypes of LGMD caused by the mutation of different genes, and now, LGMD is classified according to the results of the linkage analysis and the genes or proteins affected. Only small proportion (probably less than 10%) of LGMD is dominantly inherited, and autosomal dominant LGMD (AD-LGMD) consists of six subtypes (LGMD1A to 1F) so far. In autosomal recessive LGMD (AR-LGMD), more than 10 subtypes (LGMD2A to 2J) have been linked and most of the causative genes have been identified. Among AR-LGMDs, LGMD2A (calpain 3 deficiency), 2B (dysferlin deficiency), and sarcoglycanopathy (LGMD2C-2F) are major subtypes. The defective proteins in LGMDs are components of nuclear envelope, cytosol, sarcomere, or sarcolemma, and seem to play a different role in the pathogenesis of muscular dystrophy. It is notable that many causative genes of LGMDs are also responsible for other categories of muscular dystrophy or diseases affecting other tissue. However, by which mechanism they produce such a broad phenotypic variability is still unknown. The identification of mutation in the relevant gene is confirmative for the diagnosis, and is essential for genetic counseling and antenatal diagnosis of LGMD. Because many different genes are responsible for LGMD, differentiation of subtypes using immunohistochemistry and western blotting is the essential step toward the detection of mutation. For the effective research and medical care of the patients with muscular dystrophy in Korea, a research center with a medical facility supported by the government seems to be needed.

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Finding Rectilinear(L1), Link Metric, and Combined Shortest Paths with an Intelligent Search Method (지능형 최단 경로, 최소 꺾임 경로 및 혼합형 최단 경로 찾기)

  • Im, Jun-Sik
    • The Transactions of the Korea Information Processing Society
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    • v.3 no.1
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    • pp.43-54
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    • 1996
  • This paper presents new heuristic search algorithms for searching rectilinear r(L1), link metric, and combined shortest paths in the presence of orthogonal obstacles. The GMD(GuidedMinimum Detour) algorithm combines the best features of maze-running algorithms and line-search algorithms. The SGMD(Line-by-Line GuidedMinimum Detour)algorithm is a modiffication of the GMD algorithm that improves efficiency using line-by-line extensions. Our GMD and LGMD algorithms always find a rectilinear shortest path using the guided A search method without constructing a connection graph that contains a shortest path. The GMD and the LGMD algorithms can be implemented in O(m+eloge+NlogN) and O(eloge+NlogN) time, respectively, and O(e+N) space, where m is the total number of searched nodes, is the number of boundary sides of obstacles, and N is the total number of searched line segment. Based on the LGMD algorithm, we consider not only the problems of finding a link metric shortest path in terms of the number of bends, but also the combined L1 metric and Link Metric shortest path in terms of the length and the number of bands.

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Design of an Efficient VLSI Architecture for Collision Detection Based on Insect's Visual Interneuron (곤충의 시각 신경망 기반 충돌감지 기술의 효율적인 VLSI 구조 설계)

  • Jeong, Sooyong;Lee, Jaehyeon;Song, Deokyong;Park, Taegeun
    • The Transactions of The Korean Institute of Electrical Engineers
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    • v.67 no.12
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    • pp.1671-1677
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    • 2018
  • In this research, the collision detection system based on insect's visual interneuron has been designed. The lobula giant movement detector (LGMD) corresponds to the movement value that increases in direct collision process. If the collision is detected by the LGMD only, it could generate a crash warning even in a non-collision situation, resulting in a lot of false alarms. Directionally sensitive movement detectors (DSMD) are directionally sensitive algorithm based on the elementary movement detectors (EMD) in four directions (up, down, left, and right). In this paper, we propose an efficient VLSI architecture for a realtime collision detection system that is robust to the surrounding environment while improving accuracy. The proposed architecture is synthesized with Dongbu Hightech 110nm standard cell library and shows 333MHz of maximum operating frequency and requires 8400 gates with about 16.5KB of internal memories.

A familial case of limb-girdle muscular dystrophy with CAV3 mutation

  • Lee, Seungbok;Jang, Sesong;Shim, Youngkyu;Kim, Woo Joong;Kim, Soo Yeon;Cho, Anna;Kim, Hunmin;Kim, Jong-Il;Lim, Byung Chan;Hwang, Hee;Choi, Jieun;Kim, Ki Joong;Chae, Jong Hee
    • Journal of Genetic Medicine
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    • v.16 no.2
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    • pp.67-70
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    • 2019
  • Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical features and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical continuum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation. A 7-month-old Korean boy visited our muscle clinic because of an incidental finding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myofibers with endomysial fibrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identified a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant's pathogenicity. We performed segregation analysis and found that the patient's mother had the same variant with elevated serum CK level (972 IU/L). We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptomatic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystrophies and the additive role of muscle biopsy to confirm the variants.

Identification of a Dysferlin Gene Mutation in One Patient Showing Clinical Manifestation of Miyoshi Myopathy (미요시근육병 환자에서 밝혀진 Dysferlin 유전자 돌연변이)

  • Ji, Myung-Goo;Kim, Nam-Hee;Kim, Dae-Seong;Choi, Young-Chul
    • Annals of Clinical Neurophysiology
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    • v.11 no.2
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    • pp.59-63
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    • 2009
  • Miyoshi myopathy (MM) is caused by the mutations of dysferlin gene (DYSF), which impairs the function of dysferlin protein causing muscle membrane dysfunction. We report a patient showing the MM phenotype who has a sister with LGMD 2B phenotype, along with the results of the immunohistochemical and molecular analyses of the DYSF gene. Immunohistochemical analysis noted negative immunoreactivity against dysferlin. Direct DNA sequencing of whole exons of DYSF gene revealed heterozygous nonsense mutations (c.610C>T + c.2494C>T). To our knowledge, this is the first reported MM case with this very combination of heterozygous mutations.

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Integration of Optimality, Neural Networks, and Physiology for Field Studies of the Evolution of Visually-elicited Escape Behaviors of Orthoptera: A Minireview and Prospects

  • Shin, Hong-Sup;Jablonski, Piotr G.
    • Journal of Ecology and Environment
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    • v.31 no.2
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    • pp.89-95
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    • 2008
  • Sensing the approach of a predator is critical to the survival of prey, especially when the prey has no choice but to escape at a precisely timed moment. Escape behavior has been approached from both proximate and ultimate perspectives. On the proximate level, empirical research about electrophysiological mechanisms for detecting predators has focused on vision, an important modality that helps prey to sense approaching danger. Studies of looming-sensitive neurons in locusts are a good example of how the selective sensitivity of nervous systems towards specific targets, especially approaching objects, has been understood and realistically modeled in software and robotic systems. On the ultimate level, general optimality models have provided an evolutionary framework by considering costs and benefits of visually elicited escape responses. A recent paper showed how neural network models can be used to understand the evolution of visually mediated antipredatory behaviors. We discuss this new trend towards integration of these relatively disparate approaches, the proximate and the ultimate perspectives, for understanding of the evolution of behavior of predators and prey. Focusing on one of the best-studied escape pathway models, the Orthopteran LGMD/DCMD pathway, we discuss how ultimate-level optimality modeling can be integrated with proximate-level studies of escape behaviors in animals.

Deficiency of Anoctamin 5/TMEM16E causes nuclear positioning defect and impairs Ca2+ signaling of differentiated C2C12 myotubes

  • Phuong, Tam Thi Thanh;An, Jieun;Park, Sun Hwa;Kim, Ami;Choi, Hyun Bin;Kang, Tong Mook
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.6
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    • pp.539-547
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    • 2019
  • Anoctamin 5 (ANO5)/TMEM16E belongs to a member of the ANO/TMEM16 family member of anion channels. However, it is a matter of debate whether ANO5 functions as a genuine plasma membrane chloride channel. It has been recognized that mutations in the ANO5 gene cause many skeletal muscle diseases such as limb girdle muscular dystrophy type 2L (LGMD2L) and Miyoshi muscular dystrophy type 3 (MMD3) in human. However, the molecular mechanisms of the skeletal myopathies caused by ANO5 defects are poorly understood. To understand the role of ANO5 in skeletal muscle development and function, we silenced the ANO5 gene in C2C12 myoblasts and evaluated whether it impairs myogenesis and myotube function. ANO5 knockdown (ANO5-KD) by shRNA resulted in clustered or aggregated nuclei at the body of myotubes without affecting differentiation or myotube formation. Nuclear positioning defect of ANO5-KD myotubes was accompanied with reduced expression of Kif5b protein, a kinesin-related motor protein that controls nuclear transport during myogenesis. ANO5-KD impaired depolarization-induced $[Ca2^{+}]_i$ transient and reduced sarcoplasmic reticulum (SR) $Ca^{2+}$ storage. ANO5-KD resulted in reduced protein expression of the dihydropyridine receptor (DHPR) and SR $Ca^{2+}-ATPase$ subtype 1. In addition, ANO5-KD compromised co-localization between DHPR and ryanodine receptor subtype 1. It is concluded that ANO5-KD causes nuclear positioning defect by reduction of Kif5b expression, and compromises $Ca^{2+}$ signaling by downregulating the expression of DHPR and SERCA proteins.