ライフサイエンスコーパス: LGMD

1 LGMD 2B is caused by loss of dysferlin, a membrane repai

2 LGMD type 2C is generally associated with a more severe

3 LGMD-1C mutants of caveolin-3 (DeltaTFT or P --> L) were

4 LGMD-1C mutants of caveolin-3 behave in a dominant negat

5 In the presence of MG-132, LGMD-1C caveolin-3 mutants accumulated within the endopl

6 served in Limb-girdle muscular dystrophy-1C (LGMD-1C) in humans, characterized by a approximately 95%

7 Limb-girdle muscular dystrophy, type 2A (LGMD 2A), is an autosomal recessive disorder that causes

8 der, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been s

9 Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mu

10 Limb-girdle muscular dystrophy type 2E (LGMD 2E) is caused by mutations in the beta-sarcoglycan

11 four patients with mental retardation and a LGMD phenotype.

12 Although LGMD 2A would be a feasible candidate for gene therapy,

13 But when a TmA synapses with an LGMD it also connects laterally with another TmA.

14 Using mouse models of DMD, LGMD-2C, and LGMD-2F, we demonstrate that isolated cardiac myocytes f

15 e autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous

16 nisms underlying the pathogenesis of DMD and LGMD-1C in humans.

17 study Duchenne muscular dystrophy (DMD) and LGMD-1C, respectively, in humans.

18 overlap between the pathogenesis of hIBM and LGMD initiated by mutations in hnRNPA2B1 and DNAJB6.

19 of dysferlin, a membrane repair protein, and LGMD 2C is caused by loss of the dystrophin-associated p

20 recessive limb girdle muscular dystrophy (AR-LGMD).

21 NOS may contribute to muscle pathology in AR-LGMD with primary mutations in the sarcoglycans.

22 Because LGMD appears to receive distinct input projections, resp

23 Since any lateral interactions between LGMD inputs have always been inhibitory we may assume th

24 D, highlighting the clinical overlap between LGMD and other myopathies.

25 an important overlap in pathogenesis between LGMD and congenital muscular dystrophies, prompting furt

26 We screened 15 patients from the Brazilian LGMD patient population, 13 of whom followed a severe co

27 lar threshold computation was implemented by LGMD in all three species.

28 a multiplication operation is implemented by LGMD.

29 We investigated the computation performed by LGMD when it responds to approaching objects by recordin

30 he molecular defect in sarcoglycan-deficient LGMD is because of aberrant sarcoglycan complex assembly

31 hamster is a model for sarcoglycan-deficient LGMD with a deletion in the delta-sarcoglycan (delta-SG)

32 The lobula giant motion detector (LGMD) in the locust visual system is a wide-field, motio

33 The lobula giant motion detector (LGMD) is a wide-field bilateral visual interneuron in No

34 ron called the lobula giant motion detector (LGMD), the biophysical basis of this angular threshold c

35 The Lobula Giant Movement Detector (LGMD) is a higher-order visual interneuron of Orthoptera

36 The lobula giant movement detector (LGMD) is such a visual neuron in the locust Schistocerca

37 The lobula giant movement detector (LGMD) neuron in the locust visual system is part of a mo

38 The lobula giant movement detector (LGMD) responds preferentially to objects approaching on

39 neuron (the lobula giant movement detector, LGMD, of locusts) whose output firing rate in response t

40 nd the relative frequencies of the different LGMD subtypes.

41 Using mouse models of DMD, LGMD-2C, and LGMD-2F, we demonstrate that isolated cardi

42 cted individuals from a family with dominant LGMD and vacuolar pathology identified novel candidate m

43 girdle and congenital muscular dystrophies (LGMD and CMD) are characterized by skeletal muscle weakn

44 Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetically determine

45 zed in the limb-girdle muscular dystrophies (LGMD) has been shown to relate to the involvement of a l

46 The limb-girdle muscular dystrophies (LGMD) have recently undergone a major reclassification a

47 recessive limb-girdle muscular dystrophies (LGMDs) are genetically heterogeneous.

48 to as the limb-girdle muscular dystrophies (LGMDs) can affect boys or girls, with different types ca

49 the milder limb-girdle muscular dystrophies (LGMDs).

50 edge about limb-girdle muscular dystrophies (LGMDs).

51 including limb-girdle muscular dystrophies (LGMDs).

52 oduct of the limb girdle muscular dystrophy (LGMD) 2B locus, encodes a membrane-associated protein wi

53 hy (DMD) and limb girdle muscular dystrophy (LGMD) 2C-F result from the loss of dystrophin and the sa

54 Limb girdle muscular dystrophy (LGMD) 2F is caused by mutations in the delta-sarcoglycan

55 drome (WWS), limb girdle muscular dystrophy (LGMD) 2I and congenital muscular dystrophy 1C (MDC1C).

56 involved in limb-girdle muscular dystrophy (LGMD) and is composed of at least three proteins: alpha-

57 our types of limb-girdle muscular dystrophy (LGMD) are known to be caused by mutations in distinct sa

58 al recessive limb girdle muscular dystrophy (LGMD) is that mutations in a single sarcoglycan gene res

59 to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N).

60 is found in limb girdle muscular dystrophy (LGMD) type 2B myoblasts but not in myoblasts from patien

61 y (hIBM) and limb-girdle muscular dystrophy (LGMD), are a genetically heterogeneous group of muscle d

62 rhythmia and limb-girdle muscular dystrophy (LGMD).

63 adult onset limb girdle muscular dystrophy (LGMD).

64 mal dominant limb-girdle muscular dystrophy (LGMD-1C) in humans is due to mutations (DeltaTFT and Pro

65 mal dominant limb girdle muscular dystrophy (LGMD-1C) in humans is due to mutations within the caveol

66 nant form of limb-girdle muscular dystrophy (LGMD-1C) in humans that is due to mutations within the c

67 this form of limb girdle muscular dystrophy (LGMD-1C).

68 of the neurons that connect directly to each LGMD.

69 y-afferents (TmAs) connect the eye with each LGMD, one TmA per facet per LGMD.

70 nic mechanisms and pathways are emerging for LGMD, in particular calpainopathies, dysferlinopathies a

71 o14.6 hamster, a homologous animal model for LGMD 2F.

72 the feasibility of in vivo gene therapy for LGMD patients by using AAV vectors.

73 feasibility of sarcoglycan gene transfer for LGMD using a recombinant delta-SG adenovirus in the BIO

74 tations in the 43 kDa beta-sarcoglycan gene (LGMD 2E) were originally identified in a sporadic case o

75 he genetic understanding of the limb-girdle (LGMD) and congenital (CMD) muscular dystrophies have led

76 European and global LGMD patient registries will increase current knowledge

77 sociated with intermittent steroid dosing in LGMD 2B and 2C muscle.

78 te that dysferlin expression is perturbed in LGMD and that both mutations in the dysferlin gene and d

79 Strikingly, the phenotype in LGMD 2B patients is highly variable, but the type of mut

80 hin the first few months of life, whereas in LGMD they can occur in late childhood, adolescence or ad

81 Twelve families had mutations in known LGMD-related genes.

82 platform provides adequate coverage of known LGMD-related genes, and identify new LGMD-related genes.

83 e muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N).

84 two lobula giant movement detector neurons (LGMDs) act as looming object detectors.

85 New LGMD genes have been discovered and the clinical and gen

86 f known LGMD-related genes, and identify new LGMD-related genes.

87 sosomal inhibitors, prevented degradation of LGMD-1C caveolin-3 mutants.

88 als were to improve the genetic diagnosis of LGMD, investigate whether the WES platform provides adeq

89 computation was quite accurate: the error of LGMD and DCMD in estimating thetathres (3.1-11.9 degrees

90 ndiana Amish pedigrees with a milder form of LGMD.

91 GMD2D and represents the most common form of LGMD.

92 In other forms of LGMD, proteins have been implicated which may be importa

93 pain 3 and dysferlin genes in other forms of LGMD.

94 enlarged by the description of new forms of LGMD.

95 We found that in murine models of LGMD 2B and 2C, daily prednisone dosing reduced muscle d

96 nts a novel mechanism in the pathogenesis of LGMD 2E.

97 ations for understanding the pathogenesis of LGMD-1C at a molecular level.

98 ally derived assumptions, the firing rate of LGMD and DCMD could be shown to depend on the product ps

99 The diagnostic rate of LGMD in Australia and the relative frequencies of the di

100 d interesting studies have been published on LGMD.

101 two sporadic cases of severe childhood-onset LGMD were identified.

102 ients with LGMD2N and show that unlike other LGMD types, all patients had cognitive impairment.

103 istinguishing sarcoglycanopathies from other LGMDs or dystrophinopathies, which represent the most co

104 he eye with each LGMD, one TmA per facet per LGMD.

105 in different subtypes of autosomal recessive LGMD (the sarcoglycanopathies).

106 One type of autosomal recessive LGMD (type 2A) is caused by mutations in the protease ca

107 At least eight forms of autosomal recessive LGMD and three forms of autosomal dominant disease are n

108 ccount for four types of autosomal recessive LGMD of varying severity (types 2C through 2F), includin

109 n in the pathogenesis of autosomal recessive LGMD.

110 of genetic transmission, we demonstrate that LGMD-1C mutants of caveolin-3 behave in a dominant-negat

111 These results indicate that LGMD is a reliable neuron with which to study the biophy

112 Here, we show that LGMD-1C mutants of caveolin-3 undergo ubiquitination-pro

113 In conclusion, we show that LGMD-1C mutations lead to formation of unstable high mol

114 We have shown that LGMD-1C mutations lead to formation of unstable aggregat

115 k of this conductance minimally affected the LGMD's response to approaching stimuli, but substantiall

116 throughout the visual pathway, assessing the LGMD's activity and that of all three successive presyna

117 in large numbers and completely covering the LGMD processes.

118 pose that these retinotopic units excite the LGMD, but inhibit each other; and that the synapses form

119 show that spike frequency adaptation in the LGMD is mediated by a Ca(2+)-dependent potassium conduct

120 In the LGMD model, where different doses of vector were used, M

121 reciprocal inhibitory synapses increased the LGMD's selectivity for looming over passing objects, par

122 In this model, the LGMD multiplies postsynaptically two inputs (one excitat

123 wo-dimensional model of the responses of the LGMD based on linear summation of motion-related excitat

124 napses occur along the fine dendrites of the LGMD in the distal lobula, often in large numbers and co

125 nels act both to advance the response of the LGMD in time and to map membrane potential to firing rat

126 rns of inputs onto the dendritic tree of the LGMD, across three locust species.

127 inotopic units and along the membrane of the LGMD.

128 tory inputs within the dendritic tree of the LGMD.

129 Examining the impact of retinotopy on the LGMD's computational properties, we show that sublinear

130 al inputs impinging retinotopically onto the LGMD's dendritic fan [5-7] (Figure 1Ai).

131 activated by the approaching object onto the LGMD's dendritic tree and its membrane potential at the

132 mediately adjacent to their outputs onto the LGMD.

133 Thus, the LGMD's selectivity arises partially from presynaptic mec

134 Total excitatory input to the LGMD 1 and 2 comes from 131,000 and 186,000 synapses rea

135 ar velocity along the pathway leading to the LGMD based on the experimentally determined activation p

136 us to infer that the excitatory input to the LGMD is intrinsically directionally selective.

137 hat the retinotopic units presynaptic to the LGMD make synapses directly with each other and these sy

138 ther model, inhibition is presynaptic to the LGMD.

139 of the DNAJB6 gene, which resides within the LGMD locus at 7q36.

140 of the genes and pathogenic mechanism of the LGMDs will improve diagnostic processes and prognostic a

141 truct the network of input-synapses onto the LGMDs over spatial scales ranging from single synapses a

142 These LGMD-1C mutations lead to an approximately 95% reduction

143 Thus, LGMD might be an ideal model to investigate the biophysi

144 The mechanism by which LGMD-1C mutants of caveolin-3 are degraded remains unkno

145 -related genes not typically associated with LGMD, highlighting the clinical overlap between LGMD and

146 POMGnT1 were detected in four patients with LGMD and no evidence of brain involvement.

147 Patients with LGMD were ascertained retrospectively through the Instit

148 Patients with LGMD with a Duchenne-like severity typically had a moder

149 implications for treatment of patients with LGMD-1C.

150 ifficult-to-diagnose cohort of patients with LGMD.

151 We performed WES on 60 families with LGMDs (100 exomes).