Chromosomal Assignment of Human Nuclear Envelope Protein Genes LMNA, LMNB1, and LBR by Fluorescencein SituHybridization

Wydner, Karen L.; McNeil, John A.; Feng, Lei; Worman, Howard J.; Lawrence, Jeanne B.

doi:10.1006/geno.1996.0146

Cited by 94 publications

(70 citation statements)

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“…Two types of lamins are present in somatic cells of vertebrates. A-type lamins (lamin A, lamin C, and lamin ⌬10) are somatic cell isoforms arising by alternative splicing from the LMNA gene located on chromosome 1q21.2 (21,29,30,35,57). Lamin A and lamin C are identical over their first 566 amino acids.…”

Section: Autosomal Dominantly Inherited Missense Mutations In Lamins mentioning

confidence: 99%

Expression of a Mutant Lamin A That Causes Emery-Dreifuss Muscular Dystrophy Inhibits In Vitro Differentiation of C2C12 Myoblasts

Favreau

Higuet

Courvalin

et al. 2004

Molecular and Cellular Biology

129

101

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Autosomal dominantly inherited missense mutations in lamins A and C cause several tissue-specific diseases, including Emery-Dreifuss muscular dystrophy (EDMD) and Dunnigan-type familial partial lipodystrophy (FPLD).Here we analyze myoblast-to-myotube differentiation in C2C12 clones overexpressing lamin A mutated at arginine 453 (R453W), one of the most frequent mutations in EDMD. In contrast with clones expressing wild-type lamin A, these clones differentiate poorly or not at all, do not exit the cell cycle properly, and are extensively committed to apoptosis. These disorders are correlated with low levels of expression of transcription factor myogenin and with the persistence of a large pool of hyperphosphorylated retinoblastoma protein. Since clones mutated at arginine 482 (a site responsible for FPLD) differentiate normally, we conclude that C2C12 clones expressing R453W-mutated lamin A represent a good cellular model to study the pathophysiology of EDMD. Our hypothesis is that lamin A mutated at arginine 453 fails to build a functional scaffold and/or to maintain the chromatin compartmentation required for differentiation of myoblasts into myocytes.Lamins A and C are nuclear intermediate filament proteins that are expressed in nearly all somatic cells. Mutations in these proteins cause diseases that affect striated muscle, adipose tissue, peripheral nerves, or skeletal development (56). Hutchinson-Gilford progeria syndrome, a form of accelerated aging in childhood, has been recently shown to be due to mutations in lamin A (13, 16). Three muscular diseases, EmeryDreifuss muscular dystrophy (EDMD), dilated cardiomyopathy with conduction defect 1, and limb girdle muscular dystrophy type 1B, are dominant. Mice lacking A-type lamins or deficient in prelamin A maturation develop skeletal and cardiac lethal muscular dystrophies soon after birth, confirming the importance of A-type lamins for muscle differentiation and/or maintenance (43, 51). However, the mechanisms by which mutations in these ubiquitous proteins generate tissuespecific diseases are presently unknown.In all metazoan nuclei, lamins form a meshwork (named the nuclear lamina) located between the inner nuclear membrane and chromatin (50). Lamins interact with both integral proteins of this membrane and DNA and chromatin proteins (49, 55). Two types of lamins are present in somatic cells of vertebrates. A-type lamins (lamin A, lamin C, and lamin ⌬10) are somatic cell isoforms arising by alternative splicing from the LMNA gene located on chromosome 1q21.2 (21,29,30,35,57). Lamin A and lamin C are identical over their first 566 amino acids. A-type lamins are not expressed in early embryos or in adult stem cells and become progressively expressed during development and cell differentiation (50). B-type lamins (B1 and B2) that are encoded by different genes are constitutively expressed in all cell types (2). Like all intermediate filament proteins, lamins have a conserved central ␣-helical domain that is responsible for the formation of coiled-coil dimers f...

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Section: Autosomal Dominantly Inherited Missense Mutations In Lamins mentioning

confidence: 99%

Expression of a Mutant Lamin A That Causes Emery-Dreifuss Muscular Dystrophy Inhibits In Vitro Differentiation of C2C12 Myoblasts

Favreau

Higuet

Courvalin

et al. 2004

Molecular and Cellular Biology

129

101

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“…It is located on chromosome lq21.2-q21.3, and has a total genomic sequence length of 56.7 kb including a coding of approximately 24 kb, which contains 12 exons (Wydner et al, 1996). LMNA geneencoded protein products include lamin A and C, which are important components of the nucleus fiber layer and are the main cytoskeleton protein for maintaining normal nuclear membrane morphology.…”

Section: +mentioning

confidence: 99%

Significance of sarcomere gene mutation in patients with dilated cardiomyopathy

Zhou

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Dilated cardiomyopathy (DCM) is a myocardial disease with a high mortality rate. Approximately 40 genes have been found to be associated with DCM to date. Non-familial DCM can also be caused by gene mutations, suggesting that genetic factors were involved in the pathogenesis of DCM; therefore genetic testing is beneficial for the early diagnosis of DCM, which can facilitate the implementation of preventive measures by and within patient's families. Here, we investigated the underlying genetic mutations involved in the cause of patients with DCM. This prospective study included 240 patients with idiopathic DCM and 240 healthy volunteers. Subject clinical data were collected and polymerase chain reaction amplification was carried out on subject DNA for three candidate genes tropomyosin (TPM1), cardiac troponin T type-2 (TNNT2), and nuclear lamina protein A/C. Single nucleotide polymorphism (SNP) loci were detected in the TPM1 (rs1071646) and TNNT2 (rs3729547) genes, respectively. The genotype distributions and allele frequencies were found to satisfy Hardy-Weinberg equilibrium, which indicated that the group was representative. Statistically significant differences were found between the variant frequencies in the two SNP loci between the Kazakh patients with idiopathic DCM (IDCM) and healthy volunteers. A significant difference in the genotype distributions (P = 0.000) and allele frequencies (P = 0.000) of SNP rs1071646, and another significant difference in the genotype distributions (P = 0.000) and allele frequencies (P = 0.039) of SNP rs3729547 between Kazakhs with IDCM and Kazakh controls. These results suggest that the TPM1 (rs1071646) and TNNT2 (rs3729547) gene variants might represent risk factors for patients with DCM in the Kazakh population.

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“…LMNA is localised to chromosome 1q21 and encodes for the A-type lamins (lamin A and lamin C) arising by alternative splicing of the LMNA pre-mRNA that are expressed in most differentiated somatic cells [8,9]. Mutations in the LMNA gene cause a variety of monogenic, multisystem disorders called laminopathies that comprise such diseases as skeletal and/or cardiac muscle dystrophies, axonal neuropathy, and premature ageing syndromes as well as familial partial lipodystrophy of Dunnigan type (FPLD; OMIM 151660) [10].…”

Section: Opis Przypadkumentioning

confidence: 99%

Dunnigan-type familial partial lipodystrophy associated with the heterozygous R482W mutation in LMNA gene — case study of three women from one family

Nabrdalik

Strózik²,

Minkina-Pedras³

et al. 2013

Endokrynologia Polska

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Lipodystrophies are a heterogeneous group of diseases affecting adipose tissue distribution. Familial partial lipodystrophy of the Dunnigan type (FPLD) is a rare autosomal, dominant disorder caused by missense mutations in lamin A/C (LMNA) gene where selective loss of subcutaneous adipose tissue from the limbs and trunk, and accumulation of fat in the neck and face, is usually associated with a variety of metabolic disorders including insulin resistance, diabetes mellitus, dyslipidemia, hepatic steatosis and high blood pressure. In this report we present clinical and molecular features of three Polish women with FLPD phenotype coming from one family (a mother and her two daughters). FPLD was recognised under the circumstances of diabetes treatment, where sequencing of LMNA gene revealed heterozygous R482W mutation. In order to be able to recognise monogenic diabetes associated with lipodystrophy, it is important to be very precise in physical examination while diagnosing diabetes and to be aware of the necessity of performing genetic testing. Diabetesappropriate differential diagnosis is essential for the treatment strategy, anticipation of the disease progression, and determination of the prognosis. It is necessary for an individual mutation carrier to look carefully at the patient's family. StreszczenieLipodystrofie są heterogenną grupą chorób dotyczących rozmieszczenia tkanki tłuszczowej w organizmie. Rodzinna częściowa lipodystrofia typu Dunnigana (FPLD, familial partial lipodystrophy of the Dunnigan type) jest rzadkim autosomalnie dominującym schorzeniem, którego przyczyną jest mutacja braku sensu w genie laminy A/C (gen LMNA). W chorobie tej dochodzi do selektywnej utraty podskórnej tkanki tłuszczowej kończyn i tułowia oraz jej kumulacji w okolicy karku i twarzy, co zwykle jest związane z występowaniem różnych schorzeń metabolicznych, w tym insulinooporności, cukrzycy, dyslipidemii, stłuszczenia wątroby i nadciśnienia tętniczego. W przedstawionym raporcie opisujemy kliniczne i molekularne cechy trzech polskich kobiet pochodzących z jednej rodziny charakteryzujących się fenotypem FLPD (matka i jej dwie córki). Obecność FLPD rozpoznano w trakcie leczenia cukrzycy na podstawie sekwencjonowania genu LMNA i ujawnienia heterozygotycznej mutacji R482W. W celu rozpoznania cukrzycy monogenowej związanej z lipodystrofią ważne jest przeprowadzenie szczegółowego badania fizykalnego w toku diagnostyki cukrzycy oraz świadomość konieczności diagnostyki genetycznej wątpliwych przypadków. Prawidłowa diagnostyka różnicowa cukrzycy jest niezbędna w celu ustalenia strategii leczenia, przewidywania progresji choroby, określenia rokowania, a także jest potrzebna w celu wzmożenia czujności diagnostycznej w odniesieniu do rodziny osoby będącej nosicielem mutacji. (Endokrynol Pol 2013; 64 (4): 306-310)

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Chromosomal Assignment of Human Nuclear Envelope Protein Genes LMNA, LMNB1, and LBR by Fluorescencein SituHybridization

Cited by 94 publications

References 0 publications

Expression of a Mutant Lamin A That Causes Emery-Dreifuss Muscular Dystrophy Inhibits In Vitro Differentiation of C2C12 Myoblasts

Expression of a Mutant Lamin A That Causes Emery-Dreifuss Muscular Dystrophy Inhibits In Vitro Differentiation of C2C12 Myoblasts

Significance of sarcomere gene mutation in patients with dilated cardiomyopathy

Dunnigan-type familial partial lipodystrophy associated with the heterozygous R482W mutation in LMNA gene — case study of three women from one family

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