ライフサイエンスコーパス: LMNA

1 30P)) and Emery-Dreifuss muscular dystrophy (Lmna(-/-)).

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

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

4 and related disorders caused by mutations in LMNA.

5 nuclear lamina that directly interacts with LMNA.

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

7 A recent study finds that LMNA, a gene targeted for mutation in Hutchinson Gilford

8 ases associated to scattered mutations along LMNA, a single gene encoding A-type lamins.

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

10 The mutations in LMNA activate a cryptic splice donor site, resulting in

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

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

13 One model for disease pathogenesis of LMNA and emerin mutations is cell-specific perturbations

14 B microarrays), including EDMD patients with LMNA and emerin mutations.

15 ptional model for downstream consequences of LMNA and emerin mutations.

16 chain reaction (RT-PCR) validations in both LMNA and emerin patient muscle.

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

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

19 he localization of pU(L)34 was determined in LmnA(-/-) and LmnB1(-/-) mouse embryonic fibroblasts (ME

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

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

22 eptor (PPARgamma), a nuclear lamina protein (LMNA) and its processing endoprotease (ZMPSTE24), a kina

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

24 Mutations in LMNA are associated with the laminopathies, congenital d

25 Mutations in LMNA are variably expressed and may cause cardiomyopathy

26 Lamin A and lamin C, both products of Lmna, are key components of the nuclear lamina.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

46 f Dusp4 display heart dysfunction similar to LMNA cardiomyopathy.

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

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

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

50 monomorphic ventricular tachycardia (VT) in LMNA cardiomyopathy.

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

52 he cellular mechanisms by which mutations in LMNA cause disease have been elusive.

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

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

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

56 Mutations of lamin A/C (LMNA) cause a wide range of human disorders, including p

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

58 us mutations in the human A-type lamin gene (LMNA) cause the premature aging disease, progeria.

59 in A processing mutants, was introduced into Lmna(-/-) cells.

60 or pRB restores p16(ink4a)-responsiveness to Lmna(-/-) cells.

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

62 er the possibility that somatic mutations in LMNA contribute to tumor progression.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

78 that the two nuclear envelope defects (EDMD LMNA, EDMD emerin) were highly related disorders and wer

79 d aging disorder caused by point mutation in LMNA encoding A-type nuclear lamins.

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

81 Mutations in EMD, encoding emerin, and LMNA, encoding A-type lamins, respectively, cause X-link

82 Mutations within LMNA, encoding A-type nuclear lamins, are associated wit

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

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

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

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

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

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

89 Mutations in the LMNA gene (encoding lamin A/C) underlie familial partial

90 Mutations in the LMNA gene are linked to a variety of degenerative disord

91 Mutations in the LMNA gene are responsible for this syndrome.

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

93 The LMNA gene encodes lamins A and C, two intermediate filam

94 The human LMNA gene encodes the essential nuclear envelope protein

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

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

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

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

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

100 Mutations within the LMNA gene may therefore cause cardiomyopathy by disrupti

101 Human LMNA gene mutations result in laminopathies that include

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

103 s suspected and a mutation in exon 11 of the LMNA gene was identified.

104 on in exon 11 (residue 1824, C --> T) of the LMNA gene, activating a cryptic splice donor and resulti

105 ntermediate filament proteins encoded by the LMNA gene, are basic components of the nuclear lamina.

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

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

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

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

110 sed by mutations in codon 608 (G608G) of the LMNA gene, which activates a cryptic splice site resulti

111 Mutations in the LMNA gene, which encodes all A-type lamins, including la

112 ing disease resulting from a mutation in the LMNA gene, which encodes nuclear lamins A and C.

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

114 es, a de novo point mutation in the lamin A (LMNA) gene is the cause of HGPS.

115 by a de novo point mutation in the lamin A (LMNA) gene that results in production of a mutant lamin

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

117 to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site

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

119 ene emerin (EMD) or the autosomal lamin A/C (LMNA) gene.

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

121 kinase (MAPK) signaling cascade in hearts of Lmna H222P 'knock in' mice, a model of autosomal Emery-D

122 that we previously described in hearts from Lmna H222P knock-in mice, a model of autosomal dominant

123 We have determined the effects of an Lmna H222P mutation on signaling pathways involved in th

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

125 PD98059-treated Lmna(H222P/H222P) mice had normal cardiac ejection fract

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

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

128 We therefore treated Lmna(H222P/H222P) mice that develop cardiomyopathy with

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

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

131 Systemic treatment of Lmna(H222P/H222P) mice with PD98059 inhibited ERK phosph

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

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

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

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

136 this hypothesis, we bred mice harboring one Lmna HG allele and one Lmna LCO allele (a mutant allele

137 pothesis that the phenotypes elicited by the Lmna HG allele might be modulated by compositional chang

138 rgeted allele yielding exclusively progerin (Lmna HG) and found that heterozygous mice (Lmna HG/+) ex

139 fibroblasts had fewer misshapen nuclei than Lmna HG/+ fibroblasts (p < 0.0001).

140 CO fibroblasts and tissues was lower than in Lmna HG/+ fibroblasts and tissues.

141 roduce progerin and lamin C) with littermate Lmna HG/+ mice (which produce lamin A, lamin C, and prog

142 (Lmna HG) and found that heterozygous mice (Lmna HG/+) exhibit many phenotypes of progeria.

143 ces was uncovered; the amount of progerin in Lmna HG/LCO fibroblasts and tissues was lower than in Lm

144 We then compared the phenotypes of Lmna HG/LCO mice (which produce progerin and lamin C) wi

145 Lmna HG/LCO mice exhibited improved HG/LCO fibroblasts h

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

150 athies associated with missense mutations in LMNA is dilated cardiomyopathy with conduction system di

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

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

153 luding Hutchinson-Gilford progeria syndrome (Lmna(L530P/L530P)) and Emery-Dreifuss muscular dystrophy

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

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

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

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

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

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

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

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

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

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

164 ed mice harboring one Lmna HG allele and one Lmna LCO allele (a mutant allele that produces lamin C b

165 Remarkably, the presence of a single Lmna(LCO) allele eliminated the nuclear shape abnormalit

166 mna(LCO/LCO) mice were entirely healthy, and Lmna(LCO/LCO) cells displayed normal emerin targeting an

167 Lmna(LCO/LCO) mice were entirely healthy, and Lmna(LCO/L

168 report the development of lamin C-only mice (Lmna(LCO/LCO)), which produce lamin C but no lamin A or

169 Mutations in LMNA lead to a wide spectrum of human diseases including

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

171 LMNA maps to the well-replicated diabetes-linkage region

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

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

174 he actin filament or microtubule networks in Lmna(+/+) MEFs results in decrease of cytoplasmic elasti

175 y of a material to flow) of the cytoplasm in Lmna(-/-) MEFs are significantly reduced.

176 C deficiency in mouse embryonic fibroblasts (Lmna(-/-) MEFs) diminishes the ability of these cells to

177 ticity and viscosity down to levels found in Lmna(-/-) MEFs.

178 Mutant Lmna mice heterozygous for the disheveled hair and ears

179 In cells from Lmna -/- mice expressing exogenous lamin A, the protein

180 in the inner nuclear membrane of cells from Lmna -/- mice than in cells from wild-type mice.

181 mbryonic fibroblasts from wild-type mice and Lmna -/- mice, which lack A-type lamins.

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

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

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

185 Homozygous Lmna model "knock-in" and null mice develop cardiomyopat

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

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

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

189 The mutant LMNA mRNA and lamin A protein can be efficiently elimina

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

191 LMNA mutant cells are known to have altered biophysical

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

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

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

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

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

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

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

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

200 tified a desmin mutation, in addition to the LMNA mutation in the propositus.

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

202 The most frequent HGPS-associated LMNA mutation results in a protein, termed progerin, wit

203 ford progeria syndrome (HGPS) is caused by a LMNA mutation that leads to the synthesis of a mutant pr

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

205 icking human laminopathy associated with the LMNA mutation.

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

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

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

209 Most LMNA mutations affect skeletal and cardiac muscle by mec

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

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

212 LMNA mutations cause a variety of clinical phenotypes, i

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

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

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

216 We suggest that the dominant LMNA mutations seen in many clinically disparate laminop

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

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

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

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

221 human subjects with cardiomyopathy caused by LMNA mutations.

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

223 the pathogenesis of cardiomyopathy caused by LMNA mutations.

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

225 o treat humans with cardiomyopathy caused by LMNA mutations.

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

227 the development of cardiomyopathy caused by LMNA mutations.

228 ) compared with carriers of other pathogenic LMNA mutations.

229 interaction is affected by disease-relevant LMNA mutations.

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

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

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

233 either MyoD or, more surprisingly, desmin in Lmna(-/-) myoblasts resulted in increased differentiatio

234 hese proteins were individually expressed in Lmna(-/-) myoblasts that were then induced to undergo my

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

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

237 e by homologous recombination expressing the Lmna-N195K variant of the A-type lamins with an asparagi

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

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

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

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

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

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

244 in contrast to the nuclear fragility seen in lmna null cells, the lamina network in HGPS cells has un

245 thickness were normal even after crossing to Lmna null mice to reduce or eliminate expression of norm

246 Surprisingly, Lmna null muscle did not show the same perturbations to

247 We also analyzed the same pathways in Lmna null muscle, which shows extensive dystrophy.

248 alternative transcriptional pathways in the Lmna null myoblasts.

249 aneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the ma

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

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

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

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

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

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

256 ne-out (LOO) cross-validation approach using LMNA patient muscle as a test data set, with reverse tra

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

258 activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin

259 tionale for the existence of the 2 different Lmna products lamin A and lamin C is unclear, although s

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

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

262 ding to the known genes (TAZ, DTNA, LDB3 and LMNA), recent work has identified SCN5A, MYH7 and MYBPC3

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

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

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

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

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

268 311 individuals, blind to genotype, the QGE(LMNA) showed 100% sensitivity and 87% specificity as a p

269 and there are reported associations between LMNA single nucleotide polymorphisms (SNPs) (particularl

270 yopathy affection status and altered cardiac LMNA splicing.

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

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

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

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

275 de novo point mutation in the lamin A gene (LMNA) that activates a cryptic splice donor site, produc

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

277 an alternate splice donor site in exon 11 of LMNA (the gene encoding lamin C and prelamin A).

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

279 drome in children, is caused by mutations in LMNA (the gene for prelamin A and lamin C) that result i

280 Mutations in LMNA, the gene encoding A type lamins, cause numerous hu

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

282 years with the realization that mutations in LMNA, the gene encoding lamins A and C, cause a panoply

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

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

285 se-control or family-based associations with LMNA variants.

286 We examined the relationship between LMNA variation and type 2 diabetes (using six tag SNPs c

287 a do not therefore support a major effect of LMNA variation on diabetes risk.

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

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

290 LMNA was significantly underexpressed in mRNA from perip

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

292 G608 (GGC-->GGT) mutation within exon 11 of LMNA, which elicits a deletion of 50 aa near the C termi

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

294 It is linked to mutations in LMNA, which encodes A-type nuclear lamins.

295 uscle involvement are caused by mutations in LMNA, which encodes A-type nuclear lamins.

296 Mutations in LMNA, which encodes nuclear Lamins A and C cause disease

297 Mutations in LMNA, which encodes nuclear lamins A and C, cause a broa

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