The hot-spot lamin A R482W mutation causing familial partial lipodystrophy of Dunnigan-type (FPLD2), affects lamin A association with chromatin at the nuclear periphery and in the nuclear interior, and is associated with 3-dimensional (3D) rearrangements of chromatin. (frontiersin.org)
We discuss associated epigenetic and genome conformation changes elicited by the lamin A R482W mutation at the gene level. (frontiersin.org)
Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3-4 weeks after inducing the mutation. (bvsalud.org)
Cardiomyocyte-specific expression of the SUN1 miniprotein prevents cardiomyopathy progression, potentially avoiding the necessity of developing a specific therapeutic tailored to treating each different LMNA cardiomyopathy-inducing mutation of which there are more than 450. (bvsalud.org)
A family with dilated cardiomyopathy associated with lipodystrophy and neurological manifestations and overlapping phenotype from lamin A/C mutation was delineated in detail with a follow-up of 22 years. (medscape.com)
Sporadic cases with a mutation in the EMD gene are uncommon but are becoming increasingly more recognized in LMNA. (medscape.com)
The vast majority of circumstances are attributable to a de novo single nucleotide mutation within the LMNA gene that prompts a cryptic splice donor web site, leading to manufacturing of a poisonous type of lamin A with a 50 amino acid inner deletion, termed progerin. (eumorphia.org)
Mutations9
Mutations associated with FPL have been reported in LMNA (lamin A/C), PPARG (PPARγ), AKT2 (AKT serine/threonine kinase 2), PLIN1 (perilipin-1), and CIDEC (cell-death-inducing DFFA-like effector B). Six types (1-6) have been described. (wikipedia.org)
Type 2 (Dunnigan Variety, FPL2) is the most common form and is due to mutations in the LMNA gene. (wikipedia.org)
Type 3 is due to mutations in the PPARG gene. (wikipedia.org)
Type 6 due to mutations in the CIDEC gene. (wikipedia.org)
When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. (bvsalud.org)
Berardinelli-Seip congenital lipodystrophy type 2, the severest form of human lipodystrophy with an almost complete loss of adipose tissue, is due to loss-of-function mutations in the BSCL2/SEIPIN gene. (medscape.com)
EDMD2/EDMD3 is due to mutations (autosomal dominant and autosomal recessive, respectively) in the LMNA gene that codes for lamins A and C. Mutations in LMNA occur throughout the gene and can cause several different phenotypes (see Causes). (medscape.com)
No good data exist concerning the frequency of EMD1 or EMD2, but more than 70 different mutations have been reported in the EMD gene and more than 100 in LMNA. (medscape.com)
A European collaborative study found LMNA mutations in 18 families and 39 sporadic cases with an EMD2 phenotype. (medscape.com)
Gene4
This nucleoplasmic lamin A environment tends to be euchromatic, suggesting distinct roles of lamin A in the regulation of gene expression in peripheral and more central regions of the nucleus. (frontiersin.org)
An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. (lookformedical.com)
Emerin is a ubiquitous inner nuclear membraneprotein, presentin nearly all cell types, although its highest expression is in skeletal and cardiacmuscle.Emerin binds to many nuclear proteins, including several gene-regulatory proteins (eg, barrier-to-autointegration factor, germ cell-less, Btf), nesprins (proteins that act as molecular scaffolds), F-actin, and lamins. (medscape.com)
The first suggests that disruption of the inner nuclear membrane and the nuclear lamina causes disorganization of nuclear chromatin and gene expression, while the second proposes that the mechanical strength of the cell nucleus is disrupted when the nuclear lamina is weakened leading to structural and signaling defects in mechanically stressed tissue such as muscle and heart. (medscape.com)
Compared with other types of lipodystrophy, acquired partial lipodystrophy is seldom associated with insulin resistance and its related metabolic derangements. (medscape.com)
Disruption of SUN1's function is also accomplished by transducing and expressing a dominant-negative SUN1 miniprotein in Lmna deficient cardiomyocytes, using the cardiotrophic Adeno Associated Viral Vector 9. (bvsalud.org)
This complex includes nuclear membrane integral and associated proteins including emerin, lamin A/C, SUN1, SUN2, nesprin-1, and nesprin-2 that are proposed to form a mechanical link between the nucleoskeleton and cytoskeleton. (medscape.com)
EDMD21
The analyses in non-transformed fibroblasts show that AKTIP mislocalizes in HGPS cells but not in EDMD2. (bvsalud.org)
Familial1
The other types, such as the Kobberling-Dunnigan variety or the familial mandibuloacral dysplasia syndrome, may be familial and tend to be associated with metabolic anomalies such as glucose intolerance and hypertriglyceridemia. (medscape.com)
Autosomal dominant1
Types 1-5 are inherited in an autosomal dominant fashion. (wikipedia.org)
Progerin2
As proof of principle model combining a defined lamin alteration with a tumor cell setting, we produced HeLa cells exogenously expressing the HGPS lamin mutant progerin that alters nuclear morphology. (bvsalud.org)
This conclusion is validated by progerin-expressing HeLa cells in which nuclei are morphologically altered and AKTIP is mislocalized. (bvsalud.org)
A deoxyribonucleotide polymer that is the primary genetic material of all cells. (lookformedical.com)
Congenital1
A congenital form of DM type 1 is associated with an apparent developmental disability. (rxharun.com)
Cardiac2
As more is understood about the clinical features of the different types of LGMD, targeted management is increasingly possible, especially focusing on those patients at high risk of cardiac and respiratory complications. (bmj.com)
As our knowledge of LGMD grows, there is an increasing awareness of the complications which may accompany the various types, in particular those affecting the cardiac and respiratory systems. (bmj.com)
Nuclear membrane1
AKTIP, a protein discovered to be associated with telomeres and the nuclear membrane in interphase cells, shares sequence similarities with the ESCRT I component TSG101. (bvsalud.org)
Fibroblasts1
Radial placement of beads is determined from, here, lamin A ChIP-sequencing data in fibroblasts. (frontiersin.org)
Milder1
There are two major forms recognized based on clinical and molecular presentation: Myotonic dystrophy type I (DM1), known as Steinert disease, and myotonic dystrophy type II (DM2), or proximal myotonic myopathy which is a milder variety of DMI. (rxharun.com)
Mice1
On the behavioral stage, solely restricted and gentle alterations have been reported, with a big a part of analyzed behaviors being unaffected in GAMT KO as in contrast with wild-type mice. (eumorphia.org)
Proteins2
Since rate of autophagy in cells was not detected, it is impossible to determine, if there were changes in autophagy that were not reflected as changes in colocalization of these two proteins. (helsinki.fi)
To characterize hCMEC/D3 cells for the presence of specific endocytic pathways, proteins involved into each pathway were selected. (helsinki.fi)
Muscular3
Subsequent evaluation of this family by Emery and Dreifuss in 1966 led to distinguishing this type of X-linked dystrophy from the more severe Duchenne and Becker muscular dystrophies. (medscape.com)
Making the diagnosis of a particular type of limb girdle muscular dystrophy (LGMD) can appear challenging. (bmj.com)
Myotonic dystrophy (DM) is considered a subgroup of myopathy and the most common type of muscular dystrophy that begins in adulthood. (rxharun.com)
Nuclei1
The intensity of Beclin 1 in the nuclei was stronger than in other parts of the cell in all samples, which could indicate a stronger activity of its nuclear tasks compared to autophagy. (helsinki.fi)
Telomeres1
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. (lookformedical.com)
Form2
At the nuclear periphery, the genome is anchored to A- and B-type nuclear lamins in the form of heterochromatic lamina-associated domains. (frontiersin.org)
Another form of lipodystrophy that fits the classification of "acquired partial" not involving the complement pathway is associated with hematopoietic stem cell transplantation (HSCT) to treat leukemia or neuroblastoma. (medscape.com)
Patients1
We address recent data showing a rewiring of such interactions in cells from FPLD2 patients, and in adipose progenitor and induced pluripotent stem cell models of FPLD2. (frontiersin.org)
Pathway1
Autophagy is a pathway for cells to degrade intracellular components that are no longer needed or are detrimental for the cells. (helsinki.fi)
Found2
(B) Analysis of single cells however (e.g., by FISH) indicates that not all LADs mapped in cell populations are found at the nuclear periphery in all cells. (frontiersin.org)
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. (lookformedical.com)
Expression2
The integrated analysis of lamin expression, nuclear morphology, and AKTIP topology shows that positioning of AKTIP is influenced not only by lamin expression, but also by nuclear morphology. (bvsalud.org)
The level of cell polarization in cells grown on transwell permeable supports was characterized at multiple timepoints with four different methods: transepithelial electrical resistance (TEER) measurement, lucifer yellow permeability assay, alkaline phosphatase expression and ZO-1 expression. (helsinki.fi)
Study2
In present study we characterized human brain endothelial cells, hCMEC/D3, which are widely utilized as BBB in vitro model. (helsinki.fi)
As brain endothelial cells are polarized in vivo, the aim of the study was to demonstrate the cell polarization of hCMEC/D3 cells and to study the activity and functionality of different endocytic pathways as a function of cell polarization. (helsinki.fi)
Analysis1
After immunofluorescence staining, cells were analysed with confocal microscope and colocation analysis of Bcl-2 and Beclin 1 was performed. (helsinki.fi)
Features2
Here, we highlight features of nuclear lamin association with the genome at the nuclear periphery and in the nuclear interior. (frontiersin.org)
The specific features for each of the LGMD types, together with their particular differential diagnoses, are outlined below. (bmj.com)
Data1
CONCLUSIONS: Our data show that the combined alteration of lamin and nuclear morphology influences the localization of the tumor-associated factor AKTIP. (bvsalud.org)
Components1
BACKGROUND: Lamins, key nuclear lamina components, have been proposed as candidate risk biomarkers in different types of cancer but their accuracy is still debated. (bvsalud.org)
Unknown1
However it remains unknown which endocytic pathways are active in brain endothelial cells. (helsinki.fi)
Results2
RESULTS: In HeLa cells, AKTIP locates at less than 0.5 µm from the nuclear rim and co-localizes with lamin A/C. As compared to HeLa, there is a reduced co-localization of AKTIP with lamin A/C in both MCF7 and A549. (bvsalud.org)
The results also point to the fact that lamin alterations per se are not predictive of AKTIP mislocalization, in both non-transformed and tumor cells. (bvsalud.org)
Human1
Human embryonic kidney cells 293 (HEK-293) and hPREP knockout cell line created from them by using CRISPR/Cas9-silencing were used in the experiments. (helsinki.fi)
Rare1
Type 1 (Kobberling variety, FPL1) is very rare and has only been reported in women to date. (wikipedia.org)