ライフサイエンスコーパス: LMNA

1 n Lmna(-/-)Lap2alpha(-/-) mice compared with Lmna(-/-).

2 sed by a point mutation in the lamin A gene (LMNA).

3 a de novo point mutation at position 1824 in LMNA.

4 f ectopically expressed wild-type and mutant LMNA.

5 in vivo mechanisms of splice site choice in LMNA.

6 ts (37%): 54 (11%) Titin; 19 (4%) Lamin A/C (LMNA); 24 (5%) structural cytoskeleton-Z disk genes; 16

7 Lamins A/C are encoded by LMNA, a single heterozygous mutation of which causes Hut

8 investigate DisoFun on four exemplar genes (LMNA, ADAM15, BCL2L1 and CFLAR) with known functions at

9 we created knock-in mice harboring a mutant Lmna allele (LmnanPLAO) that yields exclusively non-farn

10 We demonstrate that 13 LMNA and 35 MYBPC3 variants identified in cardiomyopathy

11 nerated mice with germline deletions of both Lmna and Emd to determine the effects of combined loss o

12 MKL1 was caused by altered actin dynamics in Lmna(-/-) and Lmna(N195K/N195K) mutant cells.

13 Like HGPS cells, Lmna(-/-) and LmnaDelta9 fibroblasts have typically miss

14 we report in mice that lamin-A/C-deficient (Lmna(-/-)) and Lmna(N195K/N195K) mutant cells have impai

15 The Lmna null (Lmna(-/-)) and progeroid LmnaDelta9 mutant mice are mode

16 s in two AD cardiomyopathy genes, lamin A/C (LMNA) and myosin binding protein C (MYBPC3).

17 ACM was associated with variants in DSP and LMNA, and biventricular ACM with more a diverse etiology

18 orms of dilated cardiomyopathy, mutations in LMNA are responsible for a more aggressive clinical cour

19 Mutations in LMNA are variably expressed and may cause cardiomyopathy

20 Mutations in the lamin A/C gene (LMNA) are identified in patients with various types of l

21 s carrying the p.R482Q pathogenic variant in LMNA associated with Dunnigan familial partial lipodystr

22 Detailed natural history studies of LMNA-associated arrhythmic and nonarrhythmic outcomes ar

23 The phenotype is similar to LMNA-associated cardiomyopathy in humans.

24 ibition as a potential therapeutic target in LMNA-associated cardiomyopathy, for which there is no sp

25 There is no specific therapy for LMNA-associated cardiomyopathy.

26 tly different from a cohort of patients with LMNA-associated cardiomyopathy.

27 sequencing were performed in 5 control and 5 LMNA-associated DCM hearts.

28 LADs are redistributed in LMNA-associated DCM in association with markedly altered

29 Structural nuclear LMNA-associated envelope abnormalities, that is, blebs,

30 Variants in MYH7, LMNA, BAG3, TNNT2, TNNC1, PLN, ACTC1, NEXN, TPM1, and VC

31 se findings provide novel insights on mutant LMNA-based disease mechanisms and identify potential tar

32 l nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with mu

33 This is what we encountered for the LMNA c.992G>A (p.(Arg331Gln)) variant.

34 overexpresses the most common HGPS mutation (LMNA, c.1824C>T, p.G608G) in osteoblasts.

35 ockout technique, 6 individual genes (TNNT2, LMNA/C, TBX5, MYH7, ANKRD1, and NKX2.5) were knocked out

36 s exacerbated by a simultaneous reduction of LMNA/C.

37 produces an alternatively spliced product of LMNA called progerin, which is also expressed in normal

38 Mutations in the lamin A/C gene, LMNA, can cause dilated cardiomyopathy.

39 tivated ERK1/2 in hearts of a mouse model of LMNA cardiomyopathy (Lmna(H222P/H222P) mice) contributes

40 atenin contributes to the pathophysiology of LMNA cardiomyopathy and that drugs activating beta-caten

41 oskeleton contributes to the pathogenesis of LMNA cardiomyopathy and that drugs stabilizing the micro

42 Catheter ablation of VT associated with LMNA cardiomyopathy is associated with poor outcomes inc

43 IFICANCE: Revealing pathogenic mechanisms of LMNA cardiomyopathy is essential for the development of

44 gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is characterized by cardiac conduct

45 myopathy caused by lamin A/C gene mutations (LMNA cardiomyopathy) is characterized by increased myoca

46 conduction disease (hereafter referred to as LMNA cardiomyopathy).

47 Dusp4 expression is enhanced in hearts with LMNA cardiomyopathy, and its overexpression in mice caus

48 d kinase 1/2 (ERK1/2) activities in heart in LMNA cardiomyopathy, its role on the development of myoc

49 naH222P/H222P mouse, a small animal model of LMNA cardiomyopathy, suggested decreased WNT/beta-cateni

50 alpha-tubulin lead to remodeling of Cx43 in LMNA cardiomyopathy, which alters the correct communicat

51 tes in the activation of ERK1/2 signaling in LMNA cardiomyopathy.

52 fies a novel mechanism in the development of LMNA cardiomyopathy.

53 monomorphic ventricular tachycardia (VT) in LMNA cardiomyopathy.

54 ion and may contribute to the development of LMNA cardiomyopathy.

55 f Dusp4 display heart dysfunction similar to LMNA cardiomyopathy.

56 dings identify a pathogenic role of Dusp4 in LMNA cardiomyopathy.

57 delay the development from Lmna mutation to LMNA cardiomyopathy.

58 tance in the pathogenesis and progression of LMNA cardiomyopathy.

59 red distribution of Cx43 in a mouse model of LMNA cardiomyopathy.

60 Lamin A/C (LMNA) cardiomyopathy is a genetic disease with a procliv

61 the conduction abnormalities associated with LMNA-cardiomyopathy.

62 Mutations in LMNA cause degenerative disorders including the prematur

63 n the Lamin A/C (LMNA) gene-encoding nuclear LMNA cause laminopathies, which include partial lipodyst

64 Mutations in LMNA cause many human diseases, including progeria, a pr

65 Mutations in the lamin A/C gene (LMNA) cause a diverse spectrum of diseases, the most com

66 Mutations in the lamin A/C gene (LMNA) cause an autosomal dominant inherited form of dila

67 Mutations in the lamin A/C gene (LMNA) cause cardiomyopathy and also disrupt nuclear posi

68 Mutations in the lamin A/C gene (LMNA) cause several disorders referred to as laminopathi

69 LMNA chromatin immunoprecipitation-sequencing, reduced r

70 e-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, C

71 Thus, K219T-LMNA cooperates with PRC2 in downregulating SCN5A, leadi

72 henotypes in mice harboring the Lmna(nHG) or Lmna(csmHG) allele.

73 n allele yielding non-farnesylated progerin (Lmna(csmHG)) in which the carboxyl-terminal -CSIM motif

74 ncies of misshapen cell nuclei were lower in Lmna(csmHG/+) and Lmna(csmHG/csmHG) fibroblasts.

75 In contrast, Lmna(csmHG/+) and Lmna(csmHG/csmHG) mice exhibited no bo

76 cell nuclei were lower in Lmna(csmHG/+) and Lmna(csmHG/csmHG) fibroblasts.

77 In contrast, Lmna(csmHG/+) and Lmna(csmHG/csmHG) mice exhibited no bone disease and dis

78 ar mutation and cell adhesion behavior since LMNA D192G cardiomyocytes displayed loss of AFM probe-to

79 Our results suggested that the LMNA D192G mutation increased maximum nuclear deformatio

80 or of cardiomyocytes carrying the lamin A/C (LMNA) D192G mutation known to cause defective nuclear wa

81 pressing either a WT (wild type) or a mutant LMNA (D300N) protein in cardiac myocytes.

82 Administration of doxycycline suppressed LMNA(D300N) expression and prevented the phenotype.

83 Expression of LMNA(D300N) led to severe myocardial fibrosis, apoptosis

84 le-heart RNA sequencing in 2-week-old WT and LMNA(D300N) mice led to identification of ~6000 differen

85 LMNA(D300N) mutation is associated with DCM in progeroid

86 d in cardiac myocytes in mice expressing the LMNA(D300N) protein.

87 Cardiac myocyte-specific expression of LMNA(D300N), associated with DCM, led to pathogenic acti

88 338 differentially expressed genes (DEGs) in Lmna-deleted cardiomyocytes.

89 survival time 2-fold in the myocyte-specific Lmna-deleted mice.

90 companied by OM, were observed in all of the Lmna(Dhe/+) mice (100% penetrance) as early as postnatal

91 the ears or in the peritoneal macrophages of Lmna(Dhe/+) mice.

92 rophages and hyperphosphatemia were found in Lmna(Dhe/+) mutant mice.

93 The Lmna(Dhe/+) mutant mouse provides a novel model of human

94 We assessed the effects of the Lmna(Dhe/+) mutation on development of OM and pathologic

95 ous for the disheveled hair and ears allele (Lmna(Dhe/+)) exhibit early-onset, profound hearing defic

96 LMNA encodes nuclear Lamin A/C that tethers lamina-assoc

97 Mutations in LMNA encoding lamin A/C and EMD encoding emerin cause ca

98 Mutations in LMNA encoding the A-type lamins cause several diseases,

99 otype, to assess the predictive value of QGE(LMNA) for the identification of mutation carriers.

100 Excessive vascular calcification in Lmna(G609G) mice is caused by reduced extracellular accu

101 ional studies in wild-type mice and knock-in Lmna(G609G/+) mice expressing progerin, which mimic the

102 Lmna(G609G/+) mice showed excessive aortic calcification

103 ed ATP and pyrophosphate levels in plasma of Lmna(G609G/+) mice without changes in phosphorus and cal

104 Accordingly, Lmna(G609G/+) vascular smooth muscle cells are defective

105 e-mutant Lmna(G609G/G609G)Mmp13(-/-) mice or Lmna(G609G/G609G)Mmp13(+/+) mice treated with a MMP inhi

106 Importantly, double-mutant Lmna(G609G/G609G)Mmp13(-/-) mice or Lmna(G609G/G609G)Mmp

107 Mutations in the LMNA gene cause a diverse array of diseases, including d

108 Mutations in LMNA gene cause cardiomyopathy, for which mechanistic in

109 Aberrant splicing in exon 11 of the LMNA gene causes the premature aging disorder Hutchinson

110 The human LMNA gene encodes the essential nuclear envelope protein

111 es caused by dominant mutations in the human LMNA gene encoding A-type lamins.

112 e that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C).

113 Laminopathies, caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamins

114 ng quantitative gene expression (QGE) of the LMNA gene in blood and myocardium, as well as regarding

115 The reduced expression of LMNA gene in blood is a novel potential predictive bioma

116 Human LMNA gene mutations result in laminopathies that include

117 gram during metabolic stresses, highlighting Lmna gene processing as a new therapeutic target for dia

118 ndrome (HGPS) is caused by a mutation of the LMNA gene that activates a cryptic splice site.

119 Desmosomal and LMNA gene variants identify the subset of DCM patients w

120 he A-type lamins (lamin A/C), encoded by the LMNA gene, are important structural components of the nu

121 and C, alternatively spliced products of the LMNA gene, are key components of the nuclear lamina.

122 Mutations in the human LMNA gene, encoding A-type lamins, give rise to laminopa

123 Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of

124 Mutations in the LMNA gene, encoding lamins A and C, cause a variety of d

125 Mutations in the LMNA gene, encoding LMNA (lamin A/C), are responsible fo

126 in A, lamin C, and progerin, products of the Lmna gene, have antagonistic functions on energy metabol

127 er that is caused by a point mutation in the LMNA gene, resulting in production of a truncated farnes

128 syndrome, caused by a point mutation in the LMNA gene, stands out as a potential candidate.

129 are caused by >300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filame

130 issues, which are linked to mutations in the LMNA gene.

131 e by introducing frameshift mutations in the LMNA gene.

132 Lamin A/C (LMNA) gene mutations are a known cause of familial dilat

133 d by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a t

134 Mutations in the Lamin A/C (LMNA) gene-encoding nuclear LMNA cause laminopathies, wh

135 al evaluation and screening of the SCN5A and LMNA genes.

136 ed by LMNA mutation, we administered them to Lmna(H222P/H222P) mice after they developed left ventric

137 naling before the onset of cardiomyopathy in Lmna(H222P/H222P) mice prevented the development of left

138 Biochemical analysis of hearts from Lmna(H222P/H222P) mice showed enhanced p38alpha activati

139 tein kinase signaling cascade in hearts from Lmna(H222P/H222P) mice that develop dilated cardiomyopat

140 Lmna(H222P/H222P) mice were treated with ERK and JNK sig

141 Treatment of Lmna(H222P/H222P) mice with the p38alpha inhibitor ARRY-

142 rts of a mouse model of LMNA cardiomyopathy (Lmna(H222P/H222P) mice) contributes to disease, but the

143 gated the transcriptome in heart tissue from Lmna(H222P/H222P) mice, a mouse model of cardiomyopathy

144 Dusp4 is highly expressed in the hearts of Lmna(H222P/H222P) mice, and transgenic mice with cardiac

145 from these iPSCs, and which thus carry K219T-LMNA, have altered action potential, reduced peak sodium

146 Mice harboring the Lmna(HG-C) allele produced progerin in neurons, but they

147 ssue, we created a new Lmna knock-in allele, Lmna(HG-C), which produces progerin transcripts lacking

148 HGPS knock-in mice (Lmna(HG/+)) develop severe progeria-like disease phenoty

149 te a mouse model of DCM in which they delete Lmna in cardiomyocytes and discover that bromodomain and

150 The findings highlight the important role of LMNA in cardiomyocytes and identify BET bromodomain inhi

151 We report that deletion of Lmna in cardiomyocytes in mice leads to severe cardiac d

152 CT method, we evaluated the QGE of LMNA (QGE(LMNA)) in peripheral blood and myocardial RNA from carri

153 EGs) throughout the course of Lmna knockout (Lmna(-/-))-induced cardiomyopathy may reveal novel Lmna-

154 DCM related to mutations in LMNA is a common inherited cardiomyopathy that is associ

155 demonstrate that 5' splice site selection in LMNA is determined by an intricate interplay among RNA s

156 Lamin A/C (LMNA) is one of the most frequently mutated genes associ

157 te24-deficient mice carrying two copies of a Lmna knock-in allele yielding full-length prelamin A tra

158 To address that issue, we created a new Lmna knock-in allele, Lmna(HG-C), which produces progeri

159 ressed genes (DEGs) throughout the course of Lmna knockout (Lmna(-/-))-induced cardiomyopathy may rev

160 Mutations in the LMNA (lamin A/C) gene have been associated with neuromus

161 Mutations in the LMNA gene, encoding LMNA (lamin A/C), are responsible for laminopathies.

162 Mutations in LMNA (lamin A/C), which encodes lamin A and C, typically

163 The alternatively spliced products of LMNA, lamin C and prelamin A (the precursor to lamin A),

164 ed mice with a "mature lamin A-only" allele (Lmna(LAO)), which contains a stop codon immediately afte

165 r frequency of nuclear blebs was observed in Lmna(LAO/LAO) embryonic fibroblasts; however, the mature

166 Lmna(LAO/LAO) exhibited normal body weights and had no d

167 Thus, Lmna(LAO/LAO) mice synthesize mature lamin A directly, b

168 owever, the mature lamin A in the tissues of Lmna(LAO/LAO) mice was positioned normally at the nuclea

169 The levels of mature lamin A in Lmna(LAO/LAO) mice were indistinguishable from those in

170 Lifespan and body mass were increased in Lmna(-/-)Lap2alpha(-/-) mice compared with Lmna(-/-).

171 he phenotype of Lmna(-/-) mice, we generated Lmna(-/-)Lap2alpha(-/-) mice.

172 rate that aged lamin C only-expressing mice (Lmna (LCS/LCS) ) become obese but remain glucose toleran

173 ggering diabetes in young mice revealed that Lmna (LCS/LCS) animals normalize their fasting glycemia

174 biogenesis and global translational rate in Lmna (LCS/LCS) islets, two major processes involved in i

175 It is caused by a mutation in LMNA leading to expression of truncated prelamin A (prog

176 Absence of Lmna led to accumulation of 8-oxoguanine (8-oxoG) lesion

177 accumulation as a common pathogenic event in Lmna(-/-), LmnaDelta9, and HGPS disorders.

178 microscopic analyses highlighted that mutant LMNA may also lead to a morphological alteration in the

179 Lmna(-/-) MBs also exhibited increased levels of Smad2/3

180 /-))-induced cardiomyopathy may reveal novel Lmna-mediated alterations of signaling pathways leading

181 Mutant Lmna mice heterozygous for the disheveled hair and ears

182 k of age, we identified 730 and 1004 DEGs in Lmna(-/-) mice at 2 weeks and 1 month of age, respective

183 At 2 weeks, Lmna(-/-) mice demonstrated both down- and up-regulation

184 athways mediating defective muscle growth in Lmna(-/-) mice, and that inhibition of either pathway al

185 on of elevated Lap2alpha to the phenotype of Lmna(-/-) mice, we generated Lmna(-/-)Lap2alpha(-/-) mic

186 tem) cell proliferation were both reduced in Lmna(-/-) mice.

187 Lmna+/- mice also lacking emerin live to at least one ye

188 growth, heart or skeletal muscle compared to Lmna+/- mice.

189 yn in muscles attenuated NMJ deficits of HSA-Lmna-/- mice.

190 yn in muscles attenuated NMJ deficits of HSA-Lmna-/- mice.

191 s could be treated by shifting the output of LMNA more toward lamin C.

192 laminopathies and lamin A/C function is the Lmna(-/-) mouse.

193 re, we investigated mechanisms that regulate LMNA mRNA alternative splicing and assessed the feasibil

194 ope protein emerin, which is mislocalized in Lmna mutant cells and also linked to EDMD and DCM, resto

195 LMNA mutant cells are known to have altered biophysical

196 antly, reduction of SUN1 overaccumulation in LMNA mutant fibroblasts and in cells derived from HGPS p

197 In silico prediction of specific LMNA mutant-driven changes to lamin A phosphorylation an

198 he gene and protein expression in Lamin A/C (LMNA)-mutated dilated cardiolaminopathy (DCM) patients (

199 w show that cardiomyocytes from mice with an Lmna mutation and elevated cardiac ERK1/2 activity have

200 the arrhythmic and nonarrhythmic outcomes of LMNA mutation carriers and to assess the prognostic sign

201 etrospectively determined in 122 consecutive LMNA mutation carriers followed at 5 referral centers fo

202 THODS AND The multicenter cohort included 77 LMNA mutation carriers from 45 families; cardiac disorde

203 Many LMNA mutation carriers have a poor prognosis, because of

204 This facilitates selection of LMNA mutation carriers who are most likely to benefit fr

205 In this multicenter cohort of 269 LMNA mutation carriers, we evaluated risk factors for MV

206 Many patients with an LMNA mutation have neurologic symptoms by their 30s and

207 Twenty-five consecutive LMNA mutation patients from 4 centers were included (mea

208 refore prevent or delay the development from Lmna mutation to LMNA cardiomyopathy.

209 lly useful to treat cardiomyopathy caused by LMNA mutation, we administered them to Lmna(H222P/H222P)

210 In hearts of mice with LMNA mutation-induced cardiomyopathy, ERK1/2 mediated ph

211 icking human laminopathy associated with the LMNA mutation.

212 ventricular arrhythmias (MVA) in Lamin A/C (LMNA) mutation carriers.

213 of cardiomyopathy caused by lamin A/C gene (LMNA) mutation, and found that the extracellular signal-

214 athways, as a model system to understand how LMNA mutations affect nucleus-cytoskeletal connections.

215 Most LMNA mutations affect skeletal and cardiac muscle by mec

216 can be used to assess the function of novel LMNA mutations and support the idea that loss of cellula

217 tation with a phenotype reminiscent of other LMNA mutations but with a more benign course.

218 LMNA mutations cause a variety of clinical phenotypes, i

219 LMNA mutations causing cardiomyopathy elevate ERK1/2 act

220 We find that LMNA mutations causing striated muscle diseases block ac

221 Although the type of LMNA mutations have been reported to be associated with

222 Analysis of a set of LMNA mutations in a single residue, which result in thre

223 cular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for impla

224 LMNA mutations lead to degenerative disorders known as l

225 nterrelated impairment of these functions by LMNA mutations may impair the complex mechanosignaling n

226 AD-EDMD patients with LMNA mutations show the same cellular defects as the AD-

227 Human disease-causing LMNA mutations were modeled in Drosophila Lamin C (LamC)

228 Carriers of LMNA mutations with a high risk of MVA can be identified

229 We included 839 adult patients with LMNA mutations, including 660 from a French nationwide r

230 was selected for further study, because like LMNA mutations, matrin-3 has also been implicated in inh

231 al blood and myocardial RNA from carriers of LMNA mutations, versus blood and myocardial samples from

232 ) compared with carriers of other pathogenic LMNA mutations.

233 course of the disease with carriers of other LMNA mutations.

234 interaction is affected by disease-relevant LMNA mutations.

235 human subjects with cardiomyopathy caused by LMNA mutations.

236 tivity and 87% specificity as a predictor of LMNA mutations.

237 the pathogenesis of cardiomyopathy caused by LMNA mutations.

238 ed by high arrhythmogenic risk and caused by LMNA mutations.

239 o treat humans with cardiomyopathy caused by LMNA mutations.

240 rlie the pathogenesis of disorders caused by LMNA mutations.

241 the pathogenesis of cardiomyopathy caused by LMNA mutations.

242 Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopat

243 e LamC mutations were modeled after A-lamin (LMNA) mutations causing progeroid syndromes (PSs) in hum

244 We found Lap2alpha to be upregulated in Lmna(-/-) myoblasts (MBs).

245 ice that lamin-A/C-deficient (Lmna(-/-)) and Lmna(N195K/N195K) mutant cells have impaired nuclear tra

246 d by altered actin dynamics in Lmna(-/-) and Lmna(N195K/N195K) mutant cells.

247 red disease phenotypes in mice harboring the Lmna(nHG) or Lmna(csmHG) allele.

248 As expected, Lmna(nHG/+) and Lmna(nHG/nHG) mice developed severe prog

249 hypothesized that the persistent disease in Lmna(nHG/+) mice could be an unanticipated consequence o

250 t mice expressing non-farnesylated progerin (Lmna(nHG/+) mice, in which progerin's carboxyl-terminal

251 As expected, Lmna(nHG/+) and Lmna(nHG/nHG) mice developed severe progeria-like diseas

252 NCOA4-RET and LMNA-NTRK1 fusions and NRG1 and GNAS amplifications were

253 The Lmna null (Lmna(-/-)) and progeroid LmnaDelta9 mutant mi

254 BER efficiency in lamin A/C-depleted cells (Lmna null MEFs and lamin A/C-knockdown U2OS).

255 Also, Lmna null MEFs displayed reduced expression of several c

256 Lmna null mice develop these disorders and have a lifesp

257 Here we show that pathogenic mutations in LMNA or SYNE-1 responsible for severe muscle dystrophies

258 er of premature aging caused by mutations in LMNA or Zmpste24 that disrupt nuclear lamin A processing

259 Unexpectedly, Lmna(-/-) or LmnaDelta9 mice that are also deficient for

260 LMNA p.(Arg331Gln) carriers had a significantly better o

261 type, and segregation data all indicate that LMNA p.(Arg331Gln) is a pathogenic founder mutation with

262 The lipodystrophy-associated LMNA p.R482W mutation is known to impair adipogenic diff

263 uman hearts with DCM associated with defined LMNA pathogenic variants corroborated activation of the

264 shable from those in "prelamin A-only" mice (Lmna(PLAO/PLAO)), where all of the lamin A is produced f

265 ones with hydrazine gave phthalazino[6,7,8,1-lmna]pyridazino[5,4,3-gh][3,8]phenanthroline-5,11(4H,10H

266 DeltaDeltaCT method, we evaluated the QGE of LMNA (QGE(LMNA)) in peripheral blood and myocardial RNA

267 with manifestation of cardiac phenotypes in LMNA-related cardiomyopathy, suggesting that genetic ana

268 F pathway contributes to the pathogenesis of LMNA-related DCM and point to PDGF receptor-beta (PDGFRB

269 Here we modelled the LMNA-related DCM in vitro using patient-specific induced

270 LMNA-related heart disease was associated with a high in

271 iptome in skeletal muscle from patients with LMNA-related muscular dystrophy.

272 were decreased in muscles expressing mutant LMNA relative controls.

273 Mutations in LMNA result in altered nuclear morphology, but how this

274 ture ageing syndrome caused by a mutation in LMNA, resulting in a truncated form of lamin A called pr

275 311 individuals, blind to genotype, the QGE(LMNA) showed 100% sensitivity and 87% specificity as a p

276 yopathy affection status and altered cardiac LMNA splicing.

277 es associated with alterations in lamin A/C (LMNA) splicing.

278 A shared haplotype of 1 Mb around LMNA suggested a common founder.

279 ction in levels of lamin A/C or mutations in LMNA that cause an autosomal dominant premature ageing d

280 ature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A pro

281 t, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE24 cleavage site, underl

282 he past 15 years has focused on mutations in LMNA (the gene for prelamin A and lamin C) that cause pa

283 Mutations in LMNA, the gene encoding lamin A, lead to a diverse set o

284 ells carrying heterozygous K219T mutation on LMNA to develop a disease model.

285 e and subsequent alternative splicing of the LMNA transcript, as progerin induction was suppressed by

286 e lamin A-matrin-3 interface showed that the LMNA truncating mutation Delta303, which lacks the matri

287 Carriers of desmosomal and LMNA variants experienced the highest rate of SCD/VT/VF,

288 LMNA variants lead to diverse tissue-specific phenotypes

289 milial analyses of one variant, a synonymous LMNA VUS, demonstrated segregation with cardiomyopathy a

290 cher sodium azide, and as mRNA expression of LMNA was not induced by UVA.

291 LMNA was significantly underexpressed in mRNA from perip

292 Although Lmna was the only DEG down-regulated at 1 week of age, w

293 ing reference values in normal controls, QGE(LMNA) was performed in 311 consecutive patients and rela

294 Mutations in LMNA, which encodes A-type lamins, result in disparate d

295 e rare diseases associated with mutations in LMNA, which encodes nuclear lamin A/C.

296 ses of heritable DCM, including mutations in LMNA, which encodes the nuclear lamina-associated protei

297 Mutations in LMNA, which encodes the nuclear proteins Lamin A/C, can

298 Here, heterozygous sequence variants in LMNA, which result in single amino-acid substitutions, w

299 nopathy (DCM) patients (DCM(LMNAMut)) versus LMNA-wild-type DCM (DCM(LMNAWT)), and normal controls (C

300 ature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin