ライフサイエンスコーパス: mitochondrial disease

1 iagnostic work-up of patients with suspected mitochondrial disease.

2 novel ways to prevent transmission of severe mitochondrial disease.

3 s establish that COX10 mutations cause adult mitochondrial disease.

4 ssembly factor whose mutations lead to human mitochondrial disease.

5 uent respiratory chain defects seen in human mitochondrial disease.

6 should be considered, at least in part, as a mitochondrial disease.

7 complex puzzle of the genetic basis of human mitochondrial disease.

8 gulating nuclear transcription and a link to mitochondrial disease.

9 multisystem disorders known collectively as mitochondrial disease.

10 n patient care relative to manifestations of mitochondrial disease.

11 vent mtDNA loss in a human cellular model of mitochondrial disease.

12 ondrial genetics and mutations causing human mitochondrial disease.

13 e latter influences our xenocybrid models of mitochondrial disease.

14 of mutant pre-tRNAs, perhaps contributing to mitochondrial disease.

15 ous mutations in human Surf1p lead to severe mitochondrial disease.

16 ncy can recapitulate the optic neuropathy of mitochondrial disease.

17 creening of patients with cardiomyopathy for mitochondrial disease.

18 le oxidative phosphorylation attributable to mitochondrial disease.

19 (mtDNA) are central to our understanding of mitochondrial disease.

20 tRNA precursor could thus be responsible for mitochondrial disease.

21 rphologic abnormalities, all consistent with mitochondrial disease.

22 ings in the context of movement disorders in mitochondrial disease.

23 o generate a wide variety of mouse models of mitochondrial disease.

24 ons are now being studied in mouse models of mitochondrial disease.

25 ance in understanding the pathophysiology of mitochondrial disease.

26 vel and reveal a new mutational mechanism in mitochondrial disease.

27 lthy controls or 60 additional patients with mitochondrial disease.

28 is the most common pediatric presentation of mitochondrial disease.

29 complex pathological changes taking place in mitochondrial disease.

30 RNA processing have been identified to cause mitochondrial disease.

31 efect in the respiratory chain in paediatric mitochondrial disease.

32 respiratory chain deficiency associated with mitochondrial disease.

33 otyping of the movement disorders related to mitochondrial disease.

34 , the most common pediatric manifestation of mitochondrial disease.

35 ophosphatase (PPA2) that are associated with mitochondrial disease.

36 ement disorder among pediatric patients with mitochondrial disease.

37 d analysis of whole-exome sequencing data in mitochondrial disease.

38 mical phenotype observed in individuals with mitochondrial disease.

39 y optic neuropathy (LHON) is the most common mitochondrial disease.

40 P carrier AAC1 are well-recognized causes of mitochondrial disease.

41 mechanisms of neurodegeneration occurring in mitochondrial disease.

42 tissue failure, an important aspect of human mitochondrial disease.

43 s advised for the diagnosis of patients with mitochondrial disease.

44 Epilepsy is a common manifestation of mitochondrial disease.

45 to contribute to the increased mortality in mitochondrial disease.

46 ogression of epilepsy in adult patients with mitochondrial disease.

47 tic and asymptomatic mtDNA mutations causing mitochondrial diseases.

48 s, it holds broad value for the treatment of mitochondrial diseases.

49 defects in this process lead to a variety of mitochondrial diseases.

50 in Dictyostelium and human cytopathology in mitochondrial diseases.

51 ndrial nucleases can be therapeutic for some mitochondrial diseases.

52 tegy may prove relevant for a broad range of mitochondrial diseases.

53 ical heterogeneity observed in patients with mitochondrial diseases.

54 be of enormous potential benefit in treating mitochondrial diseases.

55 f Parkin expression might ameliorate certain mitochondrial diseases.

56 synthesis represent one of the few treatable mitochondrial diseases.

57 is is a promising venue for the treatment of mitochondrial diseases.

58 d its dysfunction is found in numerous human mitochondrial diseases.

59 o efficient method to treat their associated mitochondrial diseases.

60 phenotypic expression of mtDNA mutations in mitochondrial diseases.

61 have been found to be associated with known mitochondrial diseases.

62 f mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases.

63 f POLG mutations and discuss their impact on mitochondrial diseases.

64 nd cumulatively, to the progression of human mitochondrial diseases.

65 al nervous system are frequently involved in mitochondrial diseases.

66 nderstanding of the pathophysiology of human mitochondrial diseases.

67 ith partial complex I activity as models for mitochondrial diseases.

68 s for a gene therapy approach to treat human mitochondrial diseases.

69 and are involved in the pathogenesis of many mitochondrial diseases.

70 been as fast and exciting as in the area of mitochondrial diseases.

71 eleterious, consistent with studies of human mitochondrial diseases.

72 egy for therapeutic intervention in selected mitochondrial diseases.

73 lying pathogenesis of inherited and acquired mitochondrial diseases.

74 herapeutic implications for the treatment of mitochondrial diseases.

75 n POLG impede maintenance of mtDNA and cause mitochondrial diseases.

76 stem cells, even in patients with hereditary mitochondrial diseases.

77 ly highly diverse and a major cause of human mitochondrial diseases.

78 itochondrial energy generation disorders, or mitochondrial diseases.

79 the mechanisms of stress pathophysiology and mitochondrial diseases.

80 (22%), SCA6 (14%), EA2 (13%), SPG7 (10%) and mitochondrial disease (10%).

81 an [SD] age, 37 [25] years; 38% female) with mitochondrial disease (12 pediatric [age range, 4-14 yea

82 The Newcastle Mitochondrial Disease Adult Scale (NMDAS) score was meas

83 disease burden, as measured by the Newcastle Mitochondrial Disease Adult Scale, are significantly (P

84 er's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (

85 uropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and chara

86 NA) rearrangements are an important cause of mitochondrial disease and age related mitochondrial dysf

87 the copy number and organization of mtDNA in mitochondrial disease and aging, and in molecular biolog

88 -to-cell heterogeneity in cellular models of mitochondrial disease and aging.

89 cell (a.k.a., heteroplasmy) is important in mitochondrial disease and aging.

90 mtDNA) deletions are a common cause of human mitochondrial disease and also occur as part of normal a

91 DNA (mtDNA) deletions are a primary cause of mitochondrial disease and are likely to have a central r

92 he use of this approach to diagnose systemic mitochondrial disease and avoid issues associated with o

93 s of mitochondrial DNA are a common cause of mitochondrial disease and cause a broad phenotypic spect

94 f altered MICOS assembly linked with a human mitochondrial disease and confirm a central role for QIL

95 and pantothenate expand dramatically in both mitochondrial disease and control subjects.

96 ntally related to the pathophysiology of the mitochondrial disease and correlate with clinical progre

97 plain the pathogenesis of POLG2 mutations in mitochondrial disease and emphasizes the need to quantit

98 utant enzymes is important for understanding mitochondrial disease and for predicting disease severit

99 gamma (POLG) mutations are a common cause of mitochondrial disease and have also been linked to neuro

100 in human mitochondrial DNA (mtDNA) can cause mitochondrial disease and have been associated with neur

101 entifying mutations in TRMT10C as a cause of mitochondrial disease and highlighting the importance of

102 utants will be useful both in modeling human mitochondrial disease and in understanding the mechanism

103 a from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmo

104 used this assay to investigate patients with mitochondrial disease and shown in individual skeletal m

105 it will also discuss potential biomarkers of mitochondrial disease and suggest potential novel therap

106 oss was only observed in a few patients with mitochondrial disease and that all these patients had mu

107 of mterf proteins and suggest a link between mitochondrial disease and the regulation of mitochondria

108 cular, and genetic features of YARS2-related mitochondrial disease and to demonstrate a new Scottish

109 To help improve the diagnosis of mitochondrial disease and to study the mechanisms underl

110 ult) with genetic or biochemical evidence of mitochondrial disease and with 1 or more predefined extr

111 Mitochondrial diseases and aging are associated with def

112 imeric mtDNA replicase implicated in certain mitochondrial diseases and aging models.

113 They are linked with hereditary mitochondrial diseases and are often the unintended targ

114 nase complex are predominantly manifested in mitochondrial diseases and are significantly associated

115 r transition into clinical use in congenital mitochondrial diseases and chronic disorders such as typ

116 ous ophthalmologic manifestations of primary mitochondrial diseases and discusses the implications of

117 or complex I (CI) is affected in most of the mitochondrial diseases and in some neurodegenerative dis

118 ing the potential for confounding studies of mitochondrial diseases and population genetics.

119 athogenesis of SCS A-beta deficiency-related mitochondrial diseases and revealed the vital role of SC

120 Various mitochondrial diseases and syndromes could arise from de

121 en seen in the cells of patients affected by mitochondrial diseases and that also occur with age.

122 Class II mitochondrial diseases and the mitochondrion's role in a

123 ontribute to the phenotypic heterogeneity of mitochondrial disease, and may explain why some patients

124 c link between FGF21, a long-known marker of mitochondrial disease, and systemic metabolic adaptation

125 ves greater attention in relation to cancer, mitochondrial disease, and virus infection.

126 iagnostic tools and treatment strategies for mitochondrial diseases, and summarizes current understan

127 etics, as treatment of defective dynamics in mitochondrial diseases appears to be possible by improvi

128 New models for mitochondrial disease are being developed.

129 pyramidal movement disorders associated with mitochondrial disease are difficult to treat and can lea

130 Mitochondrial diseases are among the most common and mos

131 Mitochondrial diseases are among the most frequently inh

132 Mitochondrial diseases are commonly caused by mutated mi

133 Mitochondrial diseases are diverse, and animal models cu

134 Mitochondrial diseases are frequently associated with mu

135 Because mitochondrial diseases are incurable, attention has focu

136 Mitochondrial diseases are individually uncommon, but co

137 Common causes of human mitochondrial diseases are mutations affecting DNA polym

138 Mitochondrial diseases are notoriously difficult to diag

139 Mitochondrial diseases are systemic, prevalent and often

140 luding the residue mutated in a patient with mitochondrial disease, are essential for COA6 function,

141 we have developed a new paradigm in clinical mitochondrial disease assessment and management that sid

142 ate when screening for genes responsible for mitochondrial diseases associated with COX deficiency.

143 consistent with the delayed presentation of mitochondrial diseases associated with mutation of C10or

144 her underscoring the existence of a group of mitochondrial diseases associated with neurocutaneous ma

145 agement of patients with suspected or proven mitochondrial disease based on our own experience over t

146 Thus far, predicting the severity of mitochondrial disease based the magnitude of deficiency

147 xnCx(1)(0)C motif of COA6, implicating it in mitochondrial disease biology.

148 In an effort to treat mitochondrial disease, both metabolic and genetic interv

149 highlights some important recent advances in mitochondrial disease but also stresses the areas where

150 y toward preventing germline transmission of mitochondrial diseases by inducing mtDNA heteroplasmy sh

151 general strategy to treat certain classes of mitochondrial diseases by modification of the correspond

152 This review updates the topic of mitochondrial diseases by reviewing the most important r

153 this gene and demonstrates that early-onset mitochondrial disease can be caused by recurrent de novo

154 Inherited mitochondrial diseases can be caused by mutations of mit

155 Mitochondrial diseases cause a range of clinical manifes

156 e causal gene of XLSA/A and that XLSA/A is a mitochondrial disease caused by a mutation in the nuclea

157 his process is highlighted in a patient with mitochondrial disease caused by biallelic pathogenic var

158 thalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and

159 potentially useful tool for gene therapy of mitochondrial diseases caused by complex I deficiency.

160 the transgenerational transmission of human mitochondrial diseases caused by mutations in mtDNA.

161 NA of multiple primates to ascertain whether mitochondrial disease-causing sequences in humans are fi

162 f mortality in Friedreich's ataxia (FRDA), a mitochondrial disease characterized by neurodegeneration

163 e a framework for understanding cases of the mitochondrial disease citrin deficiency.

164 nquete Perinatale Francaise criteria and the Mitochondrial Disease Classification criteria, were used

165 utive adult patients attending a specialized mitochondrial disease clinic in Newcastle upon Tyne betw

166 Six adults in a well-defined mitochondrial disease cohort and 11 additional cases des

167 Mitochondrial diseases comprise a heterogeneous group of

168 g the value of nutritional interventions for mitochondrial disease conditions.

169 ay explain why some patients with underlying mitochondrial disease decompensate after seemingly trivi

170 Our understanding of mitochondrial diseases (defined restrictively as defects

171 Our understanding of mitochondrial diseases (defined restrictively as defects

172 tochondrial genetics, recent developments in mitochondrial disease diagnostic testing, and emerging i

173 e important for forensic identifications and mitochondrial disease diagnostics.

174 uclear genes for mtDNA maintenance linked to mitochondrial disease, eight heterozygous mutations (six

175 Mitochondrial diseases (encephalomyopathies) have tradit

176 At rest, patients with mitochondrial disease exhibit elevated lactate and reduc

177 gregating FBXL4 mutations in seven unrelated mitochondrial disease families, composed of six singleto

178 ical, and molecular findings in six cases of mitochondrial disease from four unrelated families affec

179 and potential novel mutations in 4 possible mitochondrial disease genes (VARS2, GARS, FLAD1, and PTC

180 hondrial research and prioritising candidate mitochondrial disease genes.

181 responsible for infantile or childhood-onset mitochondrial disease, hallmarked by the combination of

182 The phenotypic spectrum of mitochondrial disease has expanded significantly since t

183 The prevalence of mitochondrial disease has proven difficult to establish,

184 1988, a plethora of information about human mitochondrial diseases has been brought to light.

185 However, the pathophysiology of mitochondrial diseases has remained perplexing.

186 eber's hereditary optic neuropathy (LHON), a mitochondrial disease, has clinical manifestations that

187 las, no clinical trial data for treatment in mitochondrial disease have been published in the last 12

188 erstanding of the molecular genetic basis of mitochondrial disease have not only improved genetic dia

189 were responsible for clinically overt adult mitochondrial disease in 2.9 per 100,000 adults.

190 and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking

191 ene RRM2B are an important cause of familial mitochondrial disease in both adults and children and re

192 it is important to consider the diagnosis of mitochondrial disease in newborns with hypotonia and car

193 onducted at a national diagnostic center for mitochondrial disease in Newcastle upon Tyne, England, a

194 complex I replicated the hallmarks of human mitochondrial disease in the mouse.

195 Adults with suspected mitochondrial disease in the North East of England were

196 mise for discovery of new therapies to treat mitochondrial diseases in humans.

197 hus preventing or ameliorating metabolic and mitochondrial diseases in mouse models.

198 se gene and may account for up to 25% of all mitochondrial diseases in the UK and in Italy.

199 could underlie the pathophysiology of those mitochondrial diseases in which RGCs are specifically af

200 Mitochondrial diseases include a group of maternally inh

201 ations of this balance are relevant to human mitochondrial diseases including mitochondrial neurogast

202 tations have been identified in a variety of mitochondrial diseases including progressive external op

203 a confirm that the total prevalence of adult mitochondrial disease, including pathogenic mutations of

204 ainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in

205 tion are the underlying cause of a number of mitochondrial diseases, including diabetes, deafness, en

206 sequencing as a primary diagnostic test for mitochondrial diseases, including those due to mtDNA mut

207 ound in the skeletal muscle of patients with mitochondrial disease, inflammatory myopathies and sarco

208 al of the yeast NDI1 gene for the therapy of mitochondrial diseases involving complex I deficiency.

209 ma (POLG) has been linked to a wide range of mitochondrial diseases involving mutation, deletion, and

210 Mitochondrial disease is a heterogeneous group of energy

211 Primary mitochondrial disease is caused by defects in the mitoch

212 The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, su

213 Mitochondrial disease is maternally inherited and refrac

214 benefits, and the current best management of mitochondrial disease is supportive.

215 and that biallelic mutations in PPA2 cause a mitochondrial disease leading to sudden cardiac arrest i

216 tive phosphorylation defect in children with mitochondrial disease, leading to a diverse range of cli

217 amyotrophic lateral sclerosis phenotype in a mitochondrial disease led us to analyse CHCHD10 in a coh

218 stores function in a Drosophila model of the mitochondrial disease Leigh syndrome and in a Drosophila

219 l outcome of patients with m.3243A>G-related mitochondrial disease manifesting with IPO.

220 sclerosis clinical spectrum by showing that mitochondrial disease may be at the origin of some of th

221 unction in children with ASD and concomitant mitochondrial disease (MD) were compared with published

222 This mouse mitochondrial disease model provides a robust platform f

223 Motivated by mitochondrial diseases, much focus has been placed into

224 n pol gamma and examines the consequences of mitochondrial disease mutations in this region.

225 geting the T8993G mutation, which causes two mitochondrial diseases, neurogenic muscle weakness, atax

226 6% had PEO and other features of mitochondrial disease not consistent with another recogn

227 This zebrafish model of mitochondrial disease now provides unique opportunities

228 Mitochondrial diseases often exhibit tissue-specific pat

229 ncludes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders,

230 n an explosion of studies on the genetics of mitochondrial diseases over the past few years, pathogen

231 some remarkable advances in our knowledge of mitochondrial diseases over the past few years.

232 from 83 unrelated families, recruited to the Mitochondrial Disease Patient Cohort Study UK.

233 uited to the Medical Research Council Centre Mitochondrial Disease Patient Cohort, Newcastle.

234 tulating the observed pathology in the human mitochondrial disease patient who died of neonatal hyper

235 ausal role of the COA6 mutation in the human mitochondrial disease patient.

236 II-mediated electron flow allows cells from mitochondrial disease patients devoid of a functional co

237 erstanding the pathologies observed in human mitochondrial disease patients.

238 fitness variation and have implications for mitochondrial disease phenotypes that differ between the

239 that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes.

240 Hence, most patients with mitochondrial disease produced by defects in the oxidati

241 This update discusses current biomarkers of mitochondrial disease progression including metabolomics

242 l variant of ribonuclease H1 associated with mitochondrial disease, R-loops are of low abundance, and

243 onding in sequence to G167P) identified as a mitochondrial disease-related mutation in human cytochro

244 conclusion, we identified m.12955A > G as a mitochondrial disease-related mutation.

245 roducts and cellular pathways that result in mitochondrial disease remain elusive.

246 Many mitochondrial diseases remain unexplained, however, in p

247 the spectrum of the clinical presentation of mitochondrial diseases, respiratory chain defects and de

248 ed that a major factor in the progression of mitochondrial disease resulting from defects in oxidativ

249 skeletal muscle from 20 individuals without mitochondrial disease revealed that up to 25% of cells i

250 vention of IFO-induced nephrotoxicity and/or mitochondrial diseases secondary to defective C-I.

251 other essential proteins are candidates for mitochondrial disease, since the mitochondrial ribosome

252 ts (87% adults) followed up at the Newcastle mitochondrial disease specialized referral center betwee

253 esides Sod2 contribute to the Epas1(-)(/)(-) mitochondrial disease state.

254 tor 2alpha (HIF-2alpha), exhibit an apparent mitochondrial disease state.

255 rial DNA (mtDNA) helicase, co-segregate with mitochondrial diseases such as adult-onset progressive e

256 pol gamma activity have been associated with mitochondrial diseases such as Alpers syndrome and progr

257 s the sirtuins, are at the core of metabolic/mitochondrial diseases, such as obesity and diabetes, an

258 ckout libraries in human cells and models of mitochondrial disease suggests chronic hypoxia could be

259 control and eight patients with POLG-related mitochondrial disease that lacked POLG mutations.

260 acity to diagnose the heterogeneous group of mitochondrial diseases that afflict the pediatric popula

261 Our findings suggest, in this common mitochondrial disease, that IPO is an under-recognized,

262 sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also present

263 pite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive

264 rs that the more we learn about the bases of mitochondrial disease, the more complex diagnosis, treat

265 the pathophysiological mechanisms underlying mitochondrial diseases, the cellular mechanisms that pro

266 rly evident in the rapidly evolving field of mitochondrial disease: the clinician is faced with a div

267 e diagnostic testing, and emerging ideas for mitochondrial disease therapies.

268 rk for future approaches to devise effective mitochondrial disease therapies.

269 hold promise for the development of targeted mitochondrial disease therapies.

270 ion suggests that it could be considered for mitochondrial disease therapy and/or therapy in muscle d

271 ssessed the prevalence of all forms of adult mitochondrial disease to include pathogenic mutations in

272 ria of SN neurons from patients with primary mitochondrial diseases to determine whether mitochondria

273 chondrial genetics and focus on prototypical mitochondrial diseases to illustrate how primary defects

274 ensor of mitochondrial membrane potential in mitochondrial diseases was addressed.

275 to create an animal model of tissue-specific mitochondrial disease, we generated 'knockout' mice defi

276 ne expression data from mice and humans with mitochondrial diseases, we show that the ATF4 pathway is

277 an early-onset, multisystem and neurological mitochondrial disease, which should be considered as a c

278 may represent a novel therapeutic avenue for mitochondrial diseases, which remain largely untreatable

279 (mtDNA) deletions are an important cause of mitochondrial disease, while somatic mtDNA deletions cau

280 ith genetically determined m.3243A>G-related mitochondrial disease, who presented with severe symptom

281 ecent emergence of the first mouse models of mitochondrial disease will provide valuable insights int

282 polymerase gamma, are an important cause of mitochondrial disease with approximately 25% of all adul

283 To review recent data on mitochondrial diseases with emphasis on their neuro-opht

284 Q4 mutations are responsible for early-onset mitochondrial diseases with heterogeneous clinical prese

285 Numerous studies have associated mitochondrial diseases with neuro-ophthalmic manifestati

286 xpression at different levels, causing human mitochondrial diseases with pleiotropic clinical manifes

287 G MTTL1 mutation is the most common cause of mitochondrial disease; yet there is limited awareness of