A silent point mutation at position 1824 (C1824T) of the LMNA gene, generating a truncated form of lamin A (progerin), has been shown to be the cause of most cases of HGPS.
Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging.
Premature cardiac death and aging is the hallmark of Hutchinson-Gilford syndrome (HGPS), a disease caused by defined mutations in the lamin A gene leading to a shortened prelamin A protein known as progerin.
Mutations in the lamin A/C protein cause laminopathies, a heterogeneous group of disorders that include recessive axonal neuropathy (CMT2B1), Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), dilated cardiomyopathy with conduction defect, and different forms of lipodystrophy and progeria.
In this study we quantitatively compared nuclear deformation and chromatin mobility in fibroblasts from a homozygous nonsense LMNA mutation patient and a Hutchinson-Gilford progeria syndrome patient with wild type dermal fibroblasts, based on the visualization of mCitrine labeled telomere-binding protein TRF2 with light-economical imaging techniques and cytometric analyses.
The majority of HGPS cases are associated with a single point mutation in the LMNA gene that causes the production of a permanently farnesylated mutant lamin A protein termed progerin.
The inner nuclear membrane protein emerin was mislocalised upon expression of the muscular dystrophy mutants G232E, Q294P or R386K, which aberrantly assembled into nuclear aggregates, or upon expression of mutants causing progeria syndromes in vivo (lamin A del50, R471C, R527C and L530P).
Human LMNA gene mutations result in laminopathies that include Emery-Dreifuss muscular dystrophy (AD-EDMD) and Hutchinson-Gilford progeria, the premature aging syndrome (HGPS).
A mutation in the nuclear structural protein lamin A, related to Hutchinson-Gilford progeria syndrome, is reviewed specifically as the mutation results in altered nuclear structure and stiffer nuclei; animal models also suggest significantly altered vascular structure.
HGPS is almost always caused by a de novo point mutation in the lamin A gene (LMNA) that activates a cryptic splice donor site, producing a truncated mutant protein termed "progerin."
The most prevalent mutation in Hutchinson-Gilford syndrome is C1824T, which activates a cryptic splice donor site to produce an abnormal lamin A protein.
Lamin A/C mutations cause a series of human diseases, collectively called laminopathies, the most severe of which is Hutchinson Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) which arises due to an unsuccessful maturation of prelamin A.
Dunnigan-type familial partial lipodystrophy and Hutchinson-Gilford progeria syndrome are laminopathies caused by mutation in LMNA that feature atherosclerosis, which is related to proatherogenic metabolic disturbances and to the generalized process of accelerated aging, respectively.
Currently, 90% of the patients are said to have de novo point mutations in the LMNA gene that substitute cytosine with thymine and have been found in individuals with HGPS.
HGPS is caused by mutation in the Lamin-A (LMNA) gene that leads, in affected young individuals, to the accumulation of the progerin protein, usually present only in aging differentiated cells.
Furthermore, by using progeroid mice deficient in ZMPSTE24 (zinc metalloprotease STE24 homologue) involved in lamin A maturation, we have demonstrated that, besides these abnormal cellular responses to stress, dysregulation of the somatotropic axis is responsible for some of the alterations associated with progeria.
Recent studies on HGPS (due to mutations of the <i>LMNA</i> gene encoding for the nucleoskeletal proteins lamin A/C) have reported disruptions in cellular and molecular mechanisms modulating genomic stability and stem cell populations, thus giving the nuclear lamina a relevant function in nuclear organization, epigenetic regulation and in the maintenance of the stem cell pool.
Hutchinson-Gilford progeria syndrome (HGPS) is an accelerated aging disorder caused by mutations in LMNA leading to expression of a truncated prelamin A variant termed progerin.
A recent study finds that LMNA, a gene targeted for mutation in Hutchinson Gilford Progeria Syndrome, may control the onset of aging-associated decline in normal fibroblasts.
Age-related nuclear defects are caused by sporadic use, in healthy individuals, of the same cryptic splice site in lamin A whose constitutive activation causes HGPS.