scholarly journals 112 THE PRESENCE OF LAMIN A/C ANTIGENS IN PORCINE EMBRYOS

2005 ◽  
Vol 17 (2) ◽  
pp. 206
Author(s):  
K. Lee ◽  
W.L. Fodor ◽  
Z. Machaty
Keyword(s):  
Olfactory Bulb ◽  
Nuclear Envelope ◽  
Progenitor Cells ◽  
Nuclear Transfer ◽  
Type A ◽  
Lamin A ◽  
Primary Role ◽  
Nuclear Lamins ◽  
Differentiated Cells

Nuclear lamins are components of the nuclear lamina, and their primary role is to support the nuclear envelope and provide anchorage sites for the chromatin. While type B lamins are expressed in all cells, type A lamins (including lamins A and C) are developmentally regulated and expressed in differentiated cells only. There are conflicting results about the presence of lamin A/C in early mammalian embryos. Lamin A/C was found to localize in the nuclear envelope of bovine, pig, and mouse embryos, while recently it has been reported that early mouse and bovine embryos lacked lamin A/C antigens. It has also been suggested that the existence of lamin A/C in the pronuclei of mouse and bovine nuclear transfer embryos indicated faulty reprogramming. The aim of this study was to investigate the presence of lamin A/C in porcine embryos of different origins (in vivo, parthenogenetic, and nuclear transfer). Embryos of various developmental stages were collected from inseminated gilts. For the production of parthenogenetic embryos, mature oocytes were electroporated and cultured for up to seven days. Fibroblast cells served as differentiated controls; progenitor cells from the olfactory bulb of a porcine fetus were used as undifferentiated controls. Lamin A/C was visualized by immunocytochemistry. Olfactory bulb progenitor cells lacked lamin A/C (0 out of 50 cells showed staining) while all fibroblast nuclei (n = 50) reacted positively with the antibody. GV-stage oocytes, being terminally differentiated cells, also possessed lamin A/C antigens (30/30). Lamin A/C was not detectable in any of the mature oocytes examined (n = 30), but it was found in early cleavage-stage embryos [both in vivo (20/20) and parthenogenetic (30/30)] with the signal becoming weaker in blastocysts (15/15). After nuclear transfer, the lamin A/C signal from fibroblast nuclei disappeared (20/20), consistent with nuclear envelope breakdown. Later it became detectable again; all nuclear transfer embryos reconstructed with either fibroblast or progenitor cells displayed lamin A/C staining in their pronuclei and at all stages examined (n = 65). This suggests that recipient oocytes remodel the donor nuclei and reassemble the nuclear envelopes of both differentiated and undifferentiated cells with type A lamins. Activated oocytes (n = 30) and early embryos (n = 40) were then incubated in the presence of actinomycin D (an inhibitor of RNA polymerase II) or cycloheximide (a protein synthesis inhibitor) for 14 h. Lamin A/C assembly was not perturbed by either treatment, indicating that the assembly did not result from de novo gene transcription but rather from solubilized lamins already in the cytoplasm. The results imply that lamin A/C is present in early pig embryos and that its presence after nuclear transfer is not an indicator of erroneous reprogramming, unlike that reported in cattle and mouse.

55 INFLUENCE OF DONOR CELL TYPE ON THE DEVELOPMENT OF PORCINE NUCLEAR TRANSFER EMBRYOS

2006 ◽  
Vol 18 (2) ◽  
pp. 136
Author(s):  
K. Lee ◽  
W. L. Fodor ◽  
Z. Machaty
Keyword(s):  
Stem Cells ◽  
Olfactory Bulb ◽  
Progenitor Cells ◽  
Nuclear Transfer ◽  
Cell Types ◽  
Blastocyst Stage ◽  
Blastocyst Formation ◽  
Developmental Potential ◽  
Differentiated Cells ◽  
Fetal Fibroblasts

Embryonic development after nuclear transfer is very low; the majority of cloned embryos do not survive the pre-implantation stage. Recent reports indicate that the characteristics of nuclear transfer embryos depend on the type of nuclear donor cells. It has been suggested that development after nuclear transfer improves if less differentiated cells are used as nuclear donors. The aim of the present study was to investigate the developmental potential of nuclear transfer embryos reconstructed using differentiated and non-differentiated cells. Two types of non-differentiated cells, skin stem cells and olfactory bulb progenitor cells, were used; fetal fibroblasts were used as differentiated control. Prior to nuclear transfer, the differentiated state of the cells was characterized by Oct-4 immunocytochemistry (Chemicon International, Inc., Temecula, CA, USA); Oct-4 is known to be expressed by pluripotent cells only. During nuclear transfer, the cells were transferred into the perivitelline space of in vitro-matured enucleated oocytes. After fusion, reconstructed oocytes were activated by an electrical pulse followed by incubation in 10 �g/mL cycloheximide and 5 �g/mL cytochalasin B for 5 h. The embryos were subsequently cultured in NCSU-23 medium for 6 days; their developmental data were recorded and compared by ANOVA. Non-differentiated cell types showed strong Oct-4 expression, whereas the marker protein was completely absent in fetal fibroblast cells. A total of 161 embryos were reconstructed using skin stem cells, 171 embryos from olfactory bulb progenitor cells, and 189 embryos from fibroblasts. Of the skin stem cell-derived embryos, 32.9% cleaved, and during subsequent culture, 5.6% developed to the morula/blastocyst stage. In the olfactory bulb progenitor cell group, 19.8% cleaved, and the percentage of embryos that developed to the morula/blastocyst stage was 4.7%. In the control group, 22.7% cleaved; the morula/blastocyst formation was 2.6%. Embryos reconstructed from skin stem cells showed superior cleavage rate compared to embryos from the other cell types (P < 0.05). Also, morula/blastocyst formation from skin stem cells was significantly higher than that from fetal fibroblasts (P < 0.05), and morula/blastocyst formation from olfactory bulb progenitor cell-derived embryos also tended to be higher compared to control embryos (P = 0.08). Furthermore, the formation of morulae/blastocysts per cleaved embryos was the highest in embryos reconstructed with olfactory bulb progenitor cells (23.5% vs. 17.0% using skin stem cells and 11.6% using fibroblasts) implying that embryos from olfactory bulb progenitor cells may have higher developmental potential in later stages of development. The results demonstrate that nuclei of different donor cells support development to various degrees and confirm previous reports that using non-differentiated cells as nuclear donors increases the efficiency of nuclear transfer in the pig.

The expression, lamin-dependent localization and RNAi depletion phenotype for emerin inC. elegans

2002 ◽  
Vol 115 (5) ◽  
pp. 923-929 ◽  
Author(s):  
Yosef Gruenbaum ◽  
Kenneth K. Lee ◽  
Jun Liu ◽  
Merav Cohen ◽  
Katherine L. Wilson
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Growth Conditions ◽  
Rnai Phenotype ◽  
Lamin B ◽  
C Elegans ◽  
Nuclear Lamins ◽  
First Time

Emerin belongs to the LEM-domain family of nuclear membrane proteins, which are conserved in metazoans from C. elegans to humans. Loss of emerin in humans causes the X-linked form of Emery-Dreifuss muscular dystrophy(EDMD), but the disease mechanism is not understood. We have begun to address the function of emerin in C. elegans, a genetically tractable nematode. The emerin gene (emr-1) is conserved in C. elegans. We detect Ce-emerin protein in the nuclear envelopes of all cell types except sperm, and find that Ce-emerin co-immunoprecipitates with Ce-lamin from embryo lysates. We show for the first time in any organism that nuclear lamins are essential for the nuclear envelope localization of emerin during early development. We further show that four other types of nuclear envelope proteins, including fellow LEM-domain protein Ce-MAN1, as well as Ce-lamin, UNC-84 and nucleoporins do not depend on Ce-emerin for their localization. This result suggests that emerin is not essential to organize or localize the only lamin (B-type) expressed in C. elegans. We also analyzed the RNAi phenotype resulting from the loss of emerin function in C. elegans under laboratory growth conditions, and found no detectable phenotype throughout development. We propose that C. elegans is an appropriate system in which to study the molecular mechanisms of emerin function in vivo.

scholarly journals Nuclear Lamins a and B1

2000 ◽  
Vol 151 (6) ◽  
pp. 1155-1168 ◽  
Author(s):  
Robert D. Moir ◽  
Miri Yoon ◽  
Satya Khuon ◽  
Robert D. Goldman
Keyword(s):  
Green Fluorescent Protein ◽  
Nuclear Envelope ◽  
Daughter Cell ◽  
Fluorescent Protein ◽  
Lamin A ◽  
Cell Nuclei ◽  
Nuclear Lamins ◽  
Daughter Cells ◽  
Lamin B1 ◽  
Green Fluorescent

At the end of mitosis, the nuclear lamins assemble to form the nuclear lamina during nuclear envelope formation in daughter cells. We have fused A- and B-type nuclear lamins to the green fluorescent protein to study this process in living cells. The results reveal that the A- and B-type lamins exhibit different pathways of assembly. In the early stages of mitosis, both lamins are distributed throughout the cytoplasm in a diffusible (nonpolymerized) state, as demonstrated by fluorescence recovery after photobleaching (FRAP). During the anaphase-telophase transition, lamin B1 begins to become concentrated at the surface of the chromosomes. As the chromosomes reach the spindle poles, virtually all of the detectable lamin B1 has accumulated at their surfaces. Subsequently, this lamin rapidly encloses the entire perimeter of the region containing decondensing chromosomes in each daughter cell. By this time, lamin B1 has assembled into a relatively stable polymer, as indicated by FRAP analyses and insolubility in detergent/high ionic strength solutions. In contrast, the association of lamin A with the nucleus begins only after the major components of the nuclear envelope including pore complexes are assembled in daughter cells. Initially, lamin A is found in an unpolymerized state throughout the nucleoplasm of daughter cell nuclei in early G1 and only gradually becomes incorporated into the peripheral lamina during the first few hours of this stage of the cell cycle. In later stages of G1, FRAP analyses suggest that both green fluorescent protein lamins A and B1 form higher order polymers throughout interphase nuclei.

scholarly journals Single molecule analysis of lamin dynamics

2018 ◽  
Author(s):  
Leonid A. Serebryannyy ◽  
David A. Ball ◽  
Tatiana S. Karpova ◽  
Tom Misteli
Keyword(s):  
Nuclear Envelope ◽  
Single Molecule ◽  
Dynamic Properties ◽  
Clinical Manifestations ◽  
Lamin A ◽  
Kinetic Properties ◽  
Intermediate Filament Proteins ◽  
Nuclear Lamins ◽  
Cellular Environment ◽  
Associated Proteins

AbstractThe nuclear envelope (NE) is an essential cellular structure that contributes to nuclear stability, organization, and function. Mutations in NE-associated proteins result in a myriad of pathologies with widely diverse clinical manifestations, ages of onsets, and affected tissues. Notably, several hundred disease-causing mutations have been mapped to the LMNA gene, which encodes the intermediate filament proteins lamin A and C, two of the major architectural components of the nuclear envelope. However, how NE dysfunction leads to the highly variable pathologies observed in patient cells and tissues remains poorly understood. One model suggests alterations in the dynamic properties of the nuclear lamina and its associated proteins contribute to disease phenotype. Here, we describe the application of single molecule tracking (SMT) methodology to characterize the behavior of nuclear envelope transmembrane proteins (NETs) and nuclear lamins in their native cellular environment at the single molecule level. As proof-of-concept, we demonstrate by SMT that Halo-tagged lamin B1, Samp1, lamin A, and lamin A Δ50 have distinct binding and kinetic properties, and we identify several disease-relevant mutants which exhibit altered binding dynamics. SMT is also able to separately probe the dynamics of the peripheral and the nucleoplasmic populations of lamin A mutants. We suggest that SMT is a robust and sensitive method to investigate how pathogenic mutations or cellular processes affect protein dynamics at the NE.

scholarly journals Lamins in disease: why do ubiquitously expressed nuclear envelope proteins give rise to tissue-specific disease phenotypes?

2001 ◽  
Vol 114 (1) ◽  
pp. 9-19 ◽  
Author(s):  
C.J. Hutchison ◽  
M. Alvarez-Reyes ◽  
O.A. Vaughan
Keyword(s):  
Membrane Proteins ◽  
Nuclear Envelope ◽  
Dna Sequences ◽  
Genetic Disorders ◽  
Integral Membrane Proteins ◽  
Partial Lipodystrophy ◽  
Nuclear Lamins ◽  
Disease Phenotypes

The nuclear lamina is a filamentous structure composed of lamins that supports the inner nuclear membrane. Several integral membrane proteins including emerin, LBR, LAP1 and LAP2 bind to nuclear lamins in vitro and can influence lamin function and dynamics in vivo. Results from various studies suggest that lamins function in DNA replication and nuclear envelope assembly and determine the size and shape of the nuclear envelope. In addition, lamins also bind chromatin and certain DNA sequences, and might influence chromosome position. Recent evidence has revealed that mutations in A-type lamins give rise to a range of rare, but dominant, genetic disorders, including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy with conduction-system disease and Dunnigan-type familial partial lipodystrophy. An examination of how lamins A/C, emerin and other integral membrane proteins interact at the INM provides the basis for a novel model for how mutations that promote disease phenotypes are likely to influence these interactions and therefore cause cellular pathology through a combination of weakness of the lamina or altered gene expression.

scholarly journals The conserved carboxy-terminal cysteine of nuclear lamins is essential for lamin association with the nuclear envelope.

1989 ◽  
Vol 109 (5) ◽  
pp. 2003-2011 ◽  
Author(s):  
G Krohne ◽  
I Waizenegger ◽  
T H Höger
Keyword(s):  
Nuclear Envelope ◽  
Experimental System ◽  
Lamin A ◽  
Xenopus Laevis Oocytes ◽  
Partial Reduction ◽  
Carboxy Terminus ◽  
Nuclear Lamins ◽  
Stable Association ◽  
Carboxy Terminal ◽  
Helical Region

We have analyzed the interaction of soluble nuclear lamins with the nuclear envelope by microinjection of normal and mutated lamins into the cytoplasm of Xenopus laevis oocytes. Our results demonstrate that the conserved cysteine of the carboxy-terminal tetrapeptide Cys Ala/Ser Ile Met of lamins is essential for their association with the nuclear envelope. Removal of this sequence or replacement of the cysteine by serine resulted in Xenopus lamin L1 remaining in a soluble, non-envelope-associated state within the nucleus. Similar mutations of Xenopus lamin A resulted in only partial reduction of nuclear envelope association, indicating that lamin A contains additional signals that can partially compensate for the lack of the cysteine. Mammalian lamin C lacks this tetrapeptide and is not associated with the nuclear envelope in our experimental system. Cloning of the tetrapeptide Cys Ala Ile Met to the carboxy terminus of human lamin C resulted in lamin being found in a nuclear envelope-associated form in oocytes. Mutations at the amino terminus and in the alpha-helical region of lamin L1 revealed that the carboxy terminus mediates the association of lamins with the nuclear envelope; however, this alone is insufficient for maintenance of a stable association with the nuclear envelope.

scholarly journals Barrier-to-Autointegration Factor Phosphorylation on Ser-4 Regulates Emerin Binding to Lamin A In Vitro and Emerin Localization In Vivo

2006 ◽  
Vol 17 (3) ◽  
pp. 1154-1163 ◽  
Author(s):  
Luiza Bengtsson ◽  
Katherine L. Wilson
Keyword(s):  
Nuclear Envelope ◽  
Lamin A ◽  
Wild Type ◽  
Proliferating Cells ◽  
Positive Role ◽  
Double Stranded Dna ◽  
Transcription Regulators ◽  
Missense Mutant

Barrier-to-autointegration factor (BAF) is a conserved 10-kDa chromatin protein essential in proliferating cells. BAF dimers bind double-stranded DNA, histone H3, histone H1.1, lamin A, and transcription regulators, plus emerin and other LEM-domain nuclear proteins. Two-dimensional gel analysis showed that endogenous human and Xenopus BAF are posttranslationally modified by phosphorylation and potentially other modifications and that they are hyperphosphorylated during mitosis. The invariant Ser-4 residue on BAF is a major site of phosphorylation during both interphase and mitosis. In HeLa cells that overexpressed the phosphomimetic BAF missense mutant S4E, but not S4A, emerin mislocalized from the nuclear envelope, suggesting Ser-4-nonphosphorylated BAF normally promotes emerin localization at the nuclear envelope. Supporting this model, wild-type BAF but not mutant S4E enhanced emerin binding to lamin A in vitro. Thus, Ser-4-unphosphorylated BAF has a positive role in localizing emerin; this role may be disease relevant because loss or mislocalization of emerin causes Emery–Dreifuss muscular dystrophy. Our findings further suggest Ser-4 phosphorylation inhibits BAF binding to emerin and lamin A, and thereby weakens emerin–lamin interactions during both mitosis and interphase.

51 DELAYED NUCLEOLOGENESIS IN PORCINE PREIMPLANTATION EMBRYOS DEVELOPED IN VIVO AND PRODUCED BY SOMATIC CELL NUCLEAR TRANSFER

2010 ◽  
Vol 22 (1) ◽  
pp. 183
Author(s):  
R. S. Deshmukh ◽  
O. Østrup ◽  
E. Lemme ◽  
B. Peterson ◽  
A. Lucas-Hahn ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Somatic Cell ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Developmental Competence ◽  
Condensed Chromatin ◽  
Preimplantation Embryos ◽  
Metaphase Chromosomes ◽  
Cell Stage

Nucleolus is known to be a well-suited morphological marker for embryo technologies. Failure in de novo nucleolar formation during embryonic genome activation (EGA) has been observed in many species. The aim of the present study was to investigate nuclear changes and nucleolar formation during EGA in the porcine preimplantation embryos developed in vivo and produced by somatic cell nuclear transfer (SCNT). Embryos were collected at early and late 1-cell stage, 2-, 4-, and 8-cell stage, early and late blastocyst stage, fixed in 3% glutaraldehyde for 1 h, and processed for transmission electron microscopy. In vivo embryos from 1- and 2-cell stages showed electron dense, spherical nucleolar precursor bodies (NPB) in centrally located nuclei with well-developed nuclear envelope and condensed chromatin. Two 1-cell-stage embryos, however, had represented metaphase chromosomes in the periphery. At the 4-cell stage, in vivo embryos displayed fibrillo-granular nucleoli containing all 3 functional nucleolar compartments: fibrillar centers (FC), dense fibrillar component (DFC), and granular component (GC). The nuclei were centrally located, round, and had complete nuclear envelopes. The same types of nuclei and nucleoli were observed for all following stages. On the other hand, embryos produced by SCNT at early 1-cell stage showed centrally located, irregular-shaped nuclei with incomplete nuclear envelopes and condensed chromatin with large intact NPB. Exceptionally, 1 out of the 5 embryos presented a peripheral nucleus with partially condensed chromatin lacking nuclear envelope and fibrillo-granular nucleolus probably persisting from donor fibroblast. Only 2 out of 5 late-1-cell SCNT embryos showed nuclear structures. The nuclei had irregular shapes, complete nuclear membranes, and contained large NPB. At the 2- and 4-cell stages, the embryos presented central nuclei with complete nuclear envelopes. Some of the embryos showed more than one nucleus of varying shapes and sizes. The fibrillo-granular nucleoli were first observed toward the 8-cell stage. The embryos from this stage contained irregularly shaped nuclei with well-developed nuclear envelopes. The nucleoli displayed fibrillar and granular compartments in SCNT 8-cell stage embryos, but lacked the typically structured functional nucleoli observed in in vivo embryos. The absence of formation of functional nucleoli at the 4-cell stage and altered nuclear ultrastructure during the EGA in SCNT embryos, thus, may be one of the main reasons for decreased developmental competence of SCNT embryos.

scholarly journals 52 NUCLEAR REMODELING AFTER SOMATIC CELL NUCLEAR TRANSFER (SCNT) IN THE RHESUS MONKEY

2005 ◽  
Vol 17 (2) ◽  
pp. 175
Author(s):  
S. Mitalipov ◽  
J. Byrne ◽  
M. Sparman ◽  
C. Ramsey ◽  
D. Wolf
Keyword(s):  
Rhesus Monkey ◽  
Nuclear Envelope ◽  
Somatic Cell ◽  
Nuclear Transfer ◽  
Chromosome Condensation ◽  
Advanced Technology ◽  
Lamin A ◽  
Spindle Formation ◽  
Fetal Fibroblasts ◽  
Nuclear Remodeling

Successful reprogramming of somatic cell nuclei after nuclear transfer requires active remodeling by factors present in the nonactivated cytoplast. High levels of maturation promoting factor (MPF) activity are associated with this remodeling process which includes nuclear envelope breakdown (NEBD), premature chromosome condensation (PCC), and spindle formation. MPF degradation, caused by fertilization or artificial activation, is in turn required for pronuclear formation and subsequent embryonic cleavage, and involves cyclin B catalyzed proteolysis by the proteasome system. In the rhesus monkey, SCNT results in the production of cleaving embryos, but development arrests at the morula stage presumably because of abnormal or incomplete reprogramming. We undertook this pilot study to examine the timing and extent of nuclear remodeling events (NEBD, PCC) in monkey SCNT embryos. The proteasome inhibitor MG-132 was employed to avoid or delay premature MPF degradation (Zhou et al. 2003 Science 302, 1179). Monkey fetal fibroblasts employed as nuclear donor cells were fused with nonactivated cytoplasts and incubated in the presence (n = 20) or absence (control; n = 35) of MG-132. Embryos were fixed and co-labeled with DAPI (DNA) and monoclonal antibody against lamin A/C (nuclear envelope). In monkey germinal vesicle-stage oocytes (n = 5) and zygotes (n = 6), a lamin A/C signal was detected at the nuclear periphery while matured MI (n = 6) and MII (n = 12) oocytes were negative for lamin A/C staining, consistent with the absence of a nuclear membrane. Donor fetal fibroblasts arrested at the G1 stage of the cell cycle exhibited a lamin A/C signal. Minimal or no changes were observed in donor nuclei within 1 h after fusion. The majority of control SCNT embryos sampled 4 h after fusion exhibited only slight chromatin condensation; however, they failed to form metaphase chromosomes. Positive lamin A/C staining indicated the presence of intact nuclear membranes. Following activation these SCNT embryos cleaved, but arrested at the 8–16 cell stage. In initial experimentation we determined the minimal efficient concentration of MG-132 to be 5 μM, that is capable of inhibiting first polar body extrusion during the MI–MII transition. Subsequent in vitro development to the blastocyst stage (53%) of fertilized oocytes treated with 5 μM MG-132 for up to 4 h was similar to that of nontreated controls. Incubation of SCNT embryos (n = 20) for 4 h with MG-132 resulted in robust chromosome condensation, spindle formation, and weak or partial lamin A/C signal. Our observations suggest that incomplete nuclear remodeling events in monkey SCNT embryos may be due to premature MPF inactivation perhaps caused by the fusion pulse. Future studies will address the developmental potential of monkey SCNT embryos exposed to MG-132. This work was supported by NIH grant NS04330, Core Grant RR00163 and a product donation from Ares Advanced Technology, Inc.

scholarly journals Lamin and the heart

Heart ◽  
2017 ◽  
Vol 104 (6) ◽  
pp. 468-479 ◽  
Author(s):  
Gabriella Captur ◽  
Eloisa Arbustini ◽  
Gisèle Bonne ◽  
Petros Syrris ◽  
Kevin Mills ◽  
...  
Keyword(s):  
Heart Disease ◽  
Nuclear Envelope ◽  
Left Ventricular ◽  
Mitogen Activated Protein Kinase ◽  
Oral Drug ◽  
Lamin A ◽  
Imaging Features ◽  
Implantable Cardioverter Defibrillators ◽  
Clinical Scenarios

Lamins A and C are intermediate filament nuclear envelope proteins encoded by the LMNA gene. Mutations in LMNA cause autosomal dominant severe heart disease, accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive conduction system disease, arrhythmia and systolic impairment, lamin A/C heart disease is more malignant than other common DCMs due to high event rates even when the left ventricular impairment is mild. It has several phenotypic mimics, but overall it is likely to be an under-recognised cause of DCM. In certain clinical scenarios, particularly familial DCM with early conduction disease, the pretest probability of finding an LMNA mutation may be quite high.Recognising lamin A/C heart disease is important because implantable cardioverter defibrillators need to be implanted early. Promising oral drug therapies are within reach thanks to research into the mitogen-activated protein kinase (MAPK) and affiliated pathways. Personalised heart failure therapy may soon become feasible for LMNA, alongside personalised risk stratification, as variant-related differences in phenotype severity and clinical course are being steadily elucidated.Genotyping and family screening are clinically important both to confirm and to exclude LMNA mutations, but it is the three-pronged integration of such genetic information with functional data from in vivo cardiomyocyte mechanics, and pathological data from microscopy of the nuclear envelope, that is properly reshaping our LMNA knowledge base, one variant at a time. This review explains the biology of lamin A/C heart disease (genetics, structure and function of lamins), clinical presentation (diagnostic pointers, electrocardiographic and imaging features), aspects of screening and management, including current uncertainties, and future directions.

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