Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel

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.

Gentests:

Klinisch Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Multiplex ligationsabhängige Amplifikation
Bearbeitungszeit 25 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 25 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25 Tage
Probentyp genomische DNS

Verknüpfte Erkrankungen:

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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Update: 26. September 2018