Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Lamin A/C

Das LMNA-Gen kodiert ein nukleäres Matrixprotein. Mutationen sind für verschiedene Erkrankungen verantwortlich: autosomal rezessive Emery-Dreifuss muskuläre Dystrophie, autosomal dominante familiäre partielle Lipodystrophie Typ 2, autosomal dominante Gliedergürteldystrophie 1B, autosomal dominante dilatative Kardiomyopathie Typ 1A, autosomal rezessive Charcot-Marie-Tooth-Erkrankung Typ 2B1, autosomal dominantes Hutchinson-Gilford-Progerie-Syndrom und das autosomal dominante Herz-Hand-Syndrom vom Slovenischen Typ.

Diagnostik:

Clinic Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5
Probentyp genomic DNA
Clinic Untersuchungsmethoden Multiplex ligationsabhängige Amplifikation
Bearbeitungszeit 25
Probentyp genomic DNA
Clinic Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 25
Probentyp genomic DNA
Clinic Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25
Probentyp genomic DNA

Krankheiten:

Familiäre partielle Lipodystrophie Typ 2
LMNA
Malouf-Syndrom
LMNA
Dilatative Kardiomyopathie 1A
LMNA

Referenzen:

1.

Bonne G et al. (1999) Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.

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2.

Fatkin D et. al. (1999) Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.

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3.

Cao H et. al. (2000) Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy.

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4.

Flier JS et al. (2000) Pushing the envelope on lipodystrophy.

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5.

Shackleton S et. al. (2000) LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.

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6.

Brodsky GL et. al. (2000) Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement.

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7.

Speckman RA et. al. (2000) Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.

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8.

Raffaele Di Barletta M et al. (2000) Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.

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9.

Muchir A et al. (2000) Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).

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10.

Hegele RA et al. (2000) LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration.

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11.

Hegele RA et al. (2000) Genetic variation in LMNA modulates plasma leptin and indices of obesity in aboriginal Canadians.

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12.

Genschel J et al. (2000) Mutations in the LMNA gene encoding lamin A/C.

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13.

Garg A et. al. (2001) Phenotypic heterogeneity in patients with familial partial lipodystrophy (dunnigan variety) related to the site of missense mutations in lamin a/c gene.

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14.

Schmidt HH et. al. (2001) Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene.

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15.

Hegele RA et al. (2001) Common genomic variation in LMNA modulates indexes of obesity in Inuit.

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16.

Brown CA et al. (2001) Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.

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17.

Vigouroux C et. al. (2001) Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene.

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18.

De Sandre-Giovannoli A et al. (2002) Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse.

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19.

Lloyd DJ et. al. (2002) A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.

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20.

Novelli G et al. (2002) Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.

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21.

van der Kooi AJ et al. (2002) Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.

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22.

Taylor MR et. al. (2003) Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.

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23.

Caux F et. al. (2003) A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.

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24.

Charniot JC et. al. (2003) Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.

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25.

De Sandre-Giovannoli A et al. (2003) Lamin a truncation in Hutchinson-Gilford progeria.

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26.

Eriksson M et al. (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome.

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27.

Mounkes LC et al. (2003) A progeroid syndrome in mice is caused by defects in A-type lamins.

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28.

Cao H et al. (2003) LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).

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29.

Cogulu O et al. (2003) Mandibuloacral dysplasia with absent breast development.

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30.

Simha V et al. (2003) Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy.

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31.

Sébillon P et. al. (2003) Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.

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32.

None (2003) Drawing the line in progeria syndromes.

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33.

Chen L et. al. (2003) LMNA mutations in atypical Werner's syndrome.

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34.

Vigouroux C et. al. (2003) LMNA mutations in atypical Werner's syndrome.

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35.

Shen JJ et al. (2003) Mandibuloacral dysplasia caused by homozygosity for the R527H mutation in lamin A/C.

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36.

Favreau C et al. (2004) Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts.

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37.

Lammerding J et al. (2004) Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.

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38.

D'Apice MR et al. (2004) Paternal origin of LMNA mutations in Hutchinson-Gilford progeria.

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39.

Csoka AB et al. (2004) Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes.

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40.

Mercuri E et al. (2004) Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant.

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41.

Goldman RD et al. (2004) Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.

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42.

Plasilova M et al. (2004) Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome.

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43.

Navarro CL et al. (2004) Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy.

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44.

Reddel CJ et al. (2004) Lamin A expression levels are unperturbed at the normal and mutant alleles but display partial splice site selection in Hutchinson-Gilford progeria syndrome.

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45.

Broers JL et al. (2004) Decreased mechanical stiffness in LMNA-/- cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies.

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46.

Vantyghem MC et al. (2004) Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities.

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47.

Arimura T et al. (2005) Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies.

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48.

Kirschner J et al. (2005) p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria.

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49.

van Engelen BG et al. (2005) The lethal phenotype of a homozygous nonsense mutation in the lamin A/C gene.

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50.

Scaffidi P et al. (2005) Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome.

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51.

Mercuri E et al. (2005) Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene.

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52.

Wuyts W et al. (2005) Somatic and gonadal mosaicism in Hutchinson-Gilford progeria.

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53.

Navarro CL et al. (2005) Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors.

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54.

Capanni C et al. (2005) Altered pre-lamin A processing is a common mechanism leading to lipodystrophy.

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55.

Hegele R et al. (2005) LMNA mutation position predicts organ system involvement in laminopathies.

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56.

D'Amico A et al. (2005) Two patients with 'Dropped head syndrome' due to mutations in LMNA or SEPN1 genes.

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57.

Mounkes LC et. al. (2005) Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice.

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58.

Sinkovec M et al. (2005) Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly. A new type of heart-hand syndrome?

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59.

Garg A et al. (2005) A novel homozygous Ala529Val LMNA mutation in Turkish patients with mandibuloacral dysplasia.

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60.

Yang SH et al. (2005) Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation.

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61.

Van Berlo JH et al. (2005) A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors.

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62.

Glynn MW et al. (2005) Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition.

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63.

Capell BC et al. (2005) Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome.

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64.

Toth JI et al. (2005) Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes.

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65.

Jacob KN et al. (2005) Phenotypic heterogeneity in body fat distribution in patients with atypical Werner's syndrome due to heterozygous Arg133Leu lamin A/C mutation.

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66.

Mallampalli MP et al. (2005) Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome.

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67.

Huang S et al. (2005) Correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference.

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68.

Van Esch H et al. (2006) A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features.

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69.

Meune C et. al. (2006) Primary prevention of sudden death in patients with lamin A/C gene mutations.

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70.

Boguslavsky RL et al. (2006) Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy.

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71.

Frock RL et al. (2006) Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation.

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72.

Varga R et al. (2006) Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome.

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73.

Morel CF et al. (2006) A LMNA splicing mutation in two sisters with severe Dunnigan-type familial partial lipodystrophy type 2.

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74.

Scaffidi P et al. (2006) Lamin A-dependent nuclear defects in human aging.

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75.

Shumaker DK et al. (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging.

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76.

Yang SH et al. (2006) A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation.

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77.

Rudnik-Schöneborn S et al. (2007) Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy.

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78.

Capell BC et al. (2006) Human laminopathies: nuclei gone genetically awry.

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79.

Nguyen D et. al. (2007) Collagen expression in fibroblasts with a novel LMNA mutation.

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80.

Lanktree M et. al. (2007) Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660).

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81.

Benedetti S et al. (2007) Phenotypic clustering of lamin A/C mutations in neuromuscular patients.

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82.

Muchir A et al. (2007) Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.

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83.

Worman HJ et al. (2007) "Laminopathies": a wide spectrum of human diseases.

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84.

Moulson CL et al. (2007) Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.

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85.

Ben Yaou R et al. (2007) Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism?

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86.

Coffinier C et al. (2007) HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells.

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87.

Decaudain A et al. (2007) New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome.

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88.

Lombardi F et al. (2007) Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype.

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89.

Kandert S et al. (2007) Nesprin-2 giant safeguards nuclear envelope architecture in LMNA S143F progeria cells.

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90.

Kosho T et al. (2007) Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes.

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91.

Scaffidi P et al. (2008) Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing.

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92.

Zirn B et al. (2008) Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral dysplasia, progeria, and rigid spine muscular dystrophy.

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93.

Rankin J et al. (2008) Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C.

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94.

Quijano-Roy S et al. (2008) De novo LMNA mutations cause a new form of congenital muscular dystrophy.

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95.

Renou L et al. (2008) Heart-hand syndrome of Slovenian type: a new kind of laminopathy.

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96.

Yang SH et al. (2008) Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated.

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97.

Muchir A et al. (2009) Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins.

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98.

Makri S et al. (2009) Germinal mosaicism for LMNA mimics autosomal recessive congenital muscular dystrophy.

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99.

Rodriguez S et al. (2009) Increased expression of the Hutchinson-Gilford progeria syndrome truncated lamin A transcript during cell aging.

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100.

McPherson E et. al. (2009) Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation.

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101.

Garavelli L et al. (2009) Mandibuloacral dysplasia type A in childhood.

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102.

Møller DV et al. (2009) The role of Lamin A/C mutations in Danish patients with idiopathic dilated cardiomyopathy.

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103.

Haque F et al. (2010) Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes.

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104.

Małek LA et al. (2011) A new c.1621 C > G, p.R541G lamin A/C mutation in a family with DCM and regional wall motion abnormalities (akinesis/dyskinesis): genotype-phenotype correlation.

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105.

Liu GH et al. (2011) Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

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106.

Chen CY et al. (2012) Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies.

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107.

Krohne G et al. (1986) The nuclear lamins. A multigene family of proteins in evolution and differentiation.

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108.

Weber K et al. (1989) Maturation of nuclear lamin A involves a specific carboxy-terminal trimming, which removes the polyisoprenylation site from the precursor; implications for the structure of the nuclear lamina.

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109.

Lebel S et al. (1987) Lamin A is not synthesized as a larger precursor polypeptide.

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110.

McKeon FD et al. () Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins.

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111.

Fisher DZ et al. (1986) cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins.

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112.

Guilly MN et al. (1987) A human T lymphoblastic cell line lacks lamins A and C.

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113.

Sinensky M et al. (1994) The processing pathway of prelamin A.

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114.

Lin F et al. (1993) Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C.

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115.

Wydner KL et al. (1996) Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization.

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