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Nepalese Journal of Ophthalmology : a... Jan 2020Progeria also known as Hutchinson Gilford Progeria Syndrome (HGPS) (MIM176670) is a very uncommon fatal genetic untimely aging syndrome. It is characterized by retarded...
INTRODUCTION
Progeria also known as Hutchinson Gilford Progeria Syndrome (HGPS) (MIM176670) is a very uncommon fatal genetic untimely aging syndrome. It is characterized by retarded physical development, accelerated degeneration of the skin, cardiovascular and musculoskeletal abnormalities. Other features include prominent eyes, thin nose, small chin and thin lips. Eyebrow hair loss, madarosis and lagopththalmos are the common ocular manifestations.
CASE
We report a case of five year old boy with complaints of discomfort in bright light and a whitish appearance in his right eye for two months. He was accompanied by the parents. They complained of loss of eyelashes and eyebrows. In the developmental history he was normal at birth till the age of one year then they noticed gradual hair fall, delayed growth, wrinkling of skin, increase in size of head and thinning of limbs.
CONCLUSION
This is the first case report from Nepal with the ocular presentation of progeria indicating the role of ocular senescence in patients with Hutchinson Progeria Gilford Syndrome.
Topics: Alopecia; Child, Preschool; Eye; Humans; Male; Nepal; Progeria; Skin
PubMed: 32799251
DOI: 10.3126/nepjoph.v12i1.25454 -
Ageing Research Reviews Jan 2003Proline/arginine-rich end leucine-rich repeat protein (PRELP) a small leucine-rich proteoglycan (SLRP), binds type I collagen to basement membranes and type II collagen... (Review)
Review
Proline/arginine-rich end leucine-rich repeat protein (PRELP) a small leucine-rich proteoglycan (SLRP), binds type I collagen to basement membranes and type II collagen to cartilage. Evidence for lack of binding of collagen in basement membranes and cartilage of Hutchinson-Gilford progeria (HGP) cases suggests PRELP involvement in that disease. PRELP deficiency is able to account for many symptoms of HGP. Moreover, PRELP also accounts for the fact that unlike many other collagen-related diseases, HGP symptoms are not congenital. The appearance of PRELP sometime after the third month of the birth, coincides with the appearance of HGP symptoms. Hutchinson-Gilford progeria has been diagnosed in twins with a chromosomal inversion at, or very near, the site of the PRELP gene.
Topics: Animals; Collagen; Extracellular Matrix Proteins; Glycoproteins; Humans; Progeria
PubMed: 12437997
DOI: 10.1016/s1568-1637(02)00044-2 -
Indian Pediatrics Feb 1991
Topics: India; Progeria
PubMed: 2055641
DOI: No ID Found -
Medical Radiography and Photography 1953
Topics: Progeria
PubMed: 13062964
DOI: No ID Found -
Aging Mar 2021Progeria is an ultra-rare (prevalence 1 in 20 million), fatal, pediatric autosomal dominant premature aging disease caused by a mutation in the gene. This mutation...
Progeria is an ultra-rare (prevalence 1 in 20 million), fatal, pediatric autosomal dominant premature aging disease caused by a mutation in the gene. This mutation results in accumulation of a high level of an aberrant form of the nuclear membrane protein, Lamin A. This aberrant protein, termed progerin, accumulates in many tissues and is responsible for the diverse array of disease phenotypes. Children die predominantly from premature atherosclerotic cardiovascular disease. The Progeria Research Foundation's 10 International Scientific Workshop took place via webinar on November 2 and 3, 2020. Participants from 30 countries joined in this new, virtual meeting format. Patient family presentations led the program, followed by updates on Progeria's first-ever application for FDA drug approval as well as initial results from the only current Progeria clinical trial. This was followed by presentations of unpublished preclinical data on drugs in development targeting the disease-causing DNA mutation, the aberrant mRNA, progerin protein, and its downstream effector proteins. Tying bench to bedside, clinicians presented new discoveries on the natural history of disease to inform future clinical trial development and new Progeria aortic valve replacement procedures. The program engaged the Progeria research community as a single unit with a common goal - to treat and cure children with Progeria worldwide.
Topics: Disease Progression; Education; Humans; Progeria
PubMed: 33735109
DOI: 10.18632/aging.202835 -
Nature Reviews. Drug Discovery Feb 2021
Topics: Animals; Mice; Phenotype; Progeria
PubMed: 33441999
DOI: 10.1038/d41573-021-00013-x -
Sleep Medicine Feb 2020
Topics: Adult; Continuous Positive Airway Pressure; Fatigue; Humans; Male; Polysomnography; Progeria; Sleep Apnea, Obstructive; Young Adult
PubMed: 31786425
DOI: 10.1016/j.sleep.2019.08.001 -
Journal of Cachexia, Sarcopenia and... Dec 2022Fibro-adipogenic progenitors (FAPs) in the muscles have been found to interact closely with muscle progenitor/stem cells (MPCs) and facilitate muscle regeneration at...
BACKGROUND
Fibro-adipogenic progenitors (FAPs) in the muscles have been found to interact closely with muscle progenitor/stem cells (MPCs) and facilitate muscle regeneration at normal conditions. However, it is not clear how FAPs may interact with MPCs in aged muscles. Senolytics have been demonstrated to selectively eliminate senescent cells and generate therapeutic benefits on ageing and multiple age-related disease models.
METHODS
By studying the muscles and primary cells of age matched WT mice and Zmpste24 (Z24 ) mice, an accelerated ageing model for Hutchinson-Gilford progeria syndrome (HGPS), we examined the interaction between FAPs and MPCs in progeria-aged muscle, and the potential effect of senolytic drug fisetin in removing senescent FAPs and improving the function of MPCs.
RESULTS
We observed that, compared with muscles of WT mice, muscles of Z24 mice contained a significantly increased number of FAPs (2.4-fold; n > =6, P < 0.05) and decreased number of MPCs (2.8-fold; n > =6, P < 0.05). FAPs isolated from Z24 muscle contained about 44% SA-β-gal+ senescent cells, in contrast to about 3.5% senescent cells in FAPs isolated from WT muscle (n > =6, P < 0.001). The co-culture of Z24 FAPs with WT MPCs resulted in impaired proliferation and myogenesis potential of WT MPCs, with the number of BrdU positive proliferative cells being reduced for 3.3 times (n > =6, P < 0.001) and the number of myosin heavy chain (MHC)-positive myotubes being reduced for 4.5 times (n > =6, P < 0.001). The treatment of the in vitro co-culture system of Z24 FAPs and WT MPCs with the senolytic drug fisetin led to increased apoptosis of Z24 FAPs (14.5-fold; n > =6, P < 0.001) and rescued the impaired function of MPCs by increasing the number of MHC-positive myotubes for 3.1 times (n > =6, P < 0.001). Treatment of Z24 mice with fisetin in vivo was effective in reducing the number of senescent FAPs (2.2-fold, n > =6, P < 0.05) and restoring the number of muscle stem cells (2.6-fold, n > =6, P < 0.05), leading to improved muscle pathology in Z24 mice.
CONCLUSIONS
These results indicate that the application of senolytics in the progeria-aged muscles can be an efficient strategy to remove senescent cells, including senescent FAPs, which results in improved function of muscle progenitor/stem cells. The senescent FAPs can be a potential novel target for therapeutic treatment of progeria ageing related muscle diseases.
Topics: Mice; Animals; Progeria; Senotherapeutics; Adipogenesis; Satellite Cells, Skeletal Muscle; Muscle Fibers, Skeletal
PubMed: 36218080
DOI: 10.1002/jcsm.13101 -
Clinical Pediatrics Jul 1969
Topics: Bone and Bones; Child; Female; Hand; Humans; Progeria; Radiography; Skull
PubMed: 5788596
DOI: 10.1177/000992286900800716 -
Cell Jan 2014Rare diseases are powerful windows into biological processes and can serve as models for the development of therapeutic strategies. The progress made on the premature...
Rare diseases are powerful windows into biological processes and can serve as models for the development of therapeutic strategies. The progress made on the premature aging disorder Progeria is a shining example of the impact that studies of rare diseases can have.
Topics: Aging; Child; Farnesyltranstransferase; Humans; Lamin Type A; Nuclear Proteins; Progeria; Protein Precursors; Translational Research, Biomedical
PubMed: 24485450
DOI: 10.1016/j.cell.2013.12.028