scholarly journals Hutchinson-Gilford Progeria Syndrome: A Rare Genetic Disorder

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Rajat G. Panigrahi ◽  
Antarmayee Panigrahi ◽  
Poornima Vijayakumar ◽  
Priyadarshini Choudhury ◽  
Sanat K. Bhuyan ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Premature Aging ◽  
Pectus Carinatum ◽  
Genetic Syndrome ◽  
Live Births ◽  
Follow Up Study ◽  
First Case ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is a rare pediatric genetic syndrome with incidence of one per eight million live births. The disorder is characterised by premature aging, generally leading to death at approximately 13.4 years of age. This is a follow-up study of a 9-year-old male with clinical and radiographic features highly suggestive of HGPS and presented here with description of differential diagnosis and dental consideration. This is the first case report of HGPS which showed pectus carinatum structure of chest.

scholarly journals A Very Rare Case of Coronary Artery Bypass Grafting in a Progeria Child

2019 ◽  
Vol 11 (4) ◽  
pp. NP244-NP246
Author(s):  
Rui Pedro Soares Cerejo ◽  
Rui A. N. Rodrigues ◽  
José D. Martins ◽  
Carolina G. E. C. Torres ◽  
Lídia M. Sousa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Genetic Disorder ◽  
Artery Bypass ◽  
Early Death ◽  
Premature Aging ◽  
Artery Disease ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome ◽  
Vessel Coronary Artery

Hutchinson-Gilford progeria syndrome is a rare genetic disorder, characterized by progressive premature aging and early death in the first or second decade of life, usually secondary to cardiovascular events (myocardial infarction and stroke). We report a case of a 14-year-old boy with progeria syndrome and cardiac arrest due to myocardial infarction, who was submitted to an immediate coronary angiography which revealed left main stem and three-vessel coronary artery disease. A prompt double bypass coronary artery grafting surgery was performed, and, despite successful coronary reperfusion, the patient remained in coma and brain death was declared on fourth day after surgery.

Hutchinson–Gilford Progeria Syndrome (Hgps) And Application Of Gene Therapy Based Crispr/Cas Technology As A Promising Innovative Treatment Approach

2021 ◽  
Vol 15 ◽  
Author(s):  
Mekha Rajeev ◽  
Chameli Ratan ◽  
Karthik Krishnan ◽  
Meenu Vijayan
Keyword(s):  
De Novo ◽  
Treatment Approach ◽  
Genetic Disorder ◽  
Symptomatic Relief ◽  
Dominant Negative ◽  
Premature Aging ◽  
Lamin A ◽  
Promising Therapeutic Approach ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Background: Hutchinson–Gilford progeria syndrome (HGPS) also known as progeria of childhood or progeria is a rare, rapid, autosomal dominant genetic disorder characterized by premature aging which occurs shortly after birth. HGPS occurs as a result of de novo point mutation in the gene recognized as LMNA gene that encodes two proteins Lamin A protein and Lamin C protein which are the structural components of the nuclear envelope. Mutations in the gene trigger abnormal splicing and induce internal deletion of 50 amino acids leading to the development of a truncated form of Lamin A protein known as Progerin. Progerin generation can be considered as the crucial step in HGPS since the protein is highly toxic to human cells, permanently farnesylated, and exhibits variation in several biochemical and structural properties within the individual. HGPS also produces complications such as skin alterations, growth failure, atherosclerosis, hair and fat loss, and bone and joint diseases. We have also revised all relevant patents relating to Hutchinson-gilford progeria syndrome and its therapy in the current article. Method: The goal of the present review article is to provide information about Hutchinson–Gilford progeria syndrome (HGPS) and the use of CRISPR/Cas technology as a promising treatment approach in the treatment of the disease. The review also discusses about different pharmacological and non-pharmacological methods of treatment currently used for HGPS. Results : The main limitation associated with progeria is the lack of a definitive cure. The existing treatment modality provides only symptomatic relief. Therefore, it is high time to develop a therapeutic method that hastens premature aging in such patients. Conclusion: CRISPR/Cas technology is a novel gene-editing tool that allows genome editing at specific loci, and is found to be a promising therapeutic approach for the treatment of genetic disorders such as HGPS where dominant-negative mutations take place.

scholarly journals Radiological Diagnosis of a Rare Premature Aging Genetic Disorder: Progeria (Hutchinson-Gilford Syndrome)

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Haji Mohammed Nazir ◽  
Akshiitha Ramesh Baabhu ◽  
Yuvaraj Muralidharan ◽  
Seena Cheppala Rajan
Keyword(s):  
Short Stature ◽  
Genetic Disorder ◽  
Premature Aging ◽  
Facial Appearance ◽  
Skin Changes ◽  
Radiological Features ◽  
Large Head ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome ◽  
Bone Abnormalities

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare disease with a combination of short stature, bone abnormalities, premature ageing, and skin changes. Though the physical appearance of these patients is characteristic, there is little emphasis on the characteristic radiological features. In this paper, we report a 16-year-old boy with clinical and radiological features of this rare genetic disorder. He had a characteristic facial appearance with a large head, large eyes, thin nose with beaked tip, small chin, protruding ears, prominent scalp veins, and absence of hair.

scholarly journals Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Julio Aguado ◽  
Agustin Sola-Carvajal ◽  
Valeria Cancila ◽  
Gwladys Revêchon ◽  
Peh Fern Ong ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Cellular Senescence ◽  
Genetic Disorder ◽  
Premature Aging ◽  
Telomere Dysfunction ◽  
Damage Response ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

AbstractHutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo.

scholarly journals Progerin impairs 3D genome organization and induces fragile telomeres by limiting the dNTP pools

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Kychygina ◽  
Marina Dall’Osto ◽  
Joshua A. M. Allen ◽  
Jean-Charles Cadoret ◽  
Vincent Piras ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Nuclear Lamina ◽  
Replication Timing ◽  
Premature Aging ◽  
Functional Connection ◽  
3D Genome ◽  
Genome Wide ◽  
Associated Proteins ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

AbstractChromatin organization within the nuclear volume is essential to regulate many aspects of its function and to safeguard its integrity. A key player in this spatial scattering of chromosomes is the nuclear envelope (NE). The NE tethers large chromatin domains through interaction with the nuclear lamina and other associated proteins. This organization is perturbed in cells from Hutchinson–Gilford progeria syndrome (HGPS), a genetic disorder characterized by premature aging features. Here, we show that HGPS-related lamina defects trigger an altered 3D telomere organization with increased contact sites between telomeres and the nuclear lamina, and an altered telomeric chromatin state. The genome-wide replication timing signature of these cells is perturbed, with a shift to earlier replication for regions that normally replicate late. As a consequence, we detected a higher density of replication forks traveling simultaneously on DNA fibers, which relies on limiting cellular dNTP pools to support processive DNA synthesis. Remarkably, increasing dNTP levels in HGPS cells rescued fragile telomeres, and improved the replicative capacity of the cells. Our work highlights a functional connection between NE dysfunction and telomere homeostasis in the context of premature aging.

scholarly journals Metabolomic profiling revels systemic signatures of premature aging induced by Hutchinson-Gilford Progeria Syndrome

2019 ◽  
Author(s):  
Gustavo Monnerat ◽  
Geisa Paulino Caprini Evaristo ◽  
Joseph Albert Medeiros Evaristo ◽  
Caleb Guedes Miranda dos Santos ◽  
Gabriel Carneiro ◽  
...  
Keyword(s):  
Energy Use ◽  
Genetic Disorder ◽  
Accelerated Aging ◽  
Cardiovascular Complications ◽  
Premature Aging ◽  
Targeted Metabolomics ◽  
Area Under Roc Curve ◽  
Progeria Syndrome ◽  
Metabolic Biomarkers ◽  
Hutchinson Gilford Progeria Syndrome

AbstractHutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder. HGPS children present a high incidence of cardiovascular complications along with altered metabolic processes and accelerated aging process. No metabolic biomarker is known and the mechanisms underlying premature aging are not fully understood. The present study analysed plasma from six HGPS patients of both sexes (7.7±1.4 years old; mean±SD) and eight controls (8.6±2.3 years old) by LC-MS/MS in high-resolution non-targeted metabolomics (Q-Exactive Plus). Several endogenous metabolites with statistical difference were found. Multivariate statistics analysis showed a clear separation between groups. Potential novel metabolic biomarkers are identified using the multivariate area under ROC curve (AUROC) based analysis, showing an AUC value higher than 0.80 using only two metabolites, and reaching 1.00 when increasing the number of metabolites in the AUROC model. Targeted metabolomics was used to validate some of the metabolites identified by the non-targeted method. Taken together, changed metabolic pathways in that panel involve sphingolipid, amino acid, and oxidation of fatty acids among others. In conclusion our data show significant alterations in cellular energy use and availability, in signal transduction, and in lipid metabolites, creating new insights on metabolic alterations associated with premature aging.

Towards a Drosophila model of Hutchinson–Gilford progeria syndrome

2008 ◽  
Vol 36 (6) ◽  
pp. 1389-1392 ◽  
Author(s):  
Gemma S. Beard ◽  
Joanna M. Bridger ◽  
Ian R. Kill ◽  
David R.P. Tree
Keyword(s):  
Drosophila Melanogaster ◽  
Premature Aging ◽  
Lamin A ◽  
Wild Type ◽  
Drosophila Model ◽  
Numerous Cell ◽  
Cellular Abnormalities ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome ◽  
Adult Drosophila

The laminopathy Hutchinson–Gilford progeria syndrome (HGPS) is caused by the mutant lamin A protein progerin and leads to premature aging of affected children. Despite numerous cell biological and biochemical insights into the basis for the cellular abnormalities seen in HGPS, the mechanism linking progerin to the organismal phenotype is not fully understood. To begin to address the mechanism behind HGPS using Drosophila melanogaster, we have ectopically expressed progerin and lamin A. We found that ectopic progerin and lamin A phenocopy several effects of laminopathies in developing and adult Drosophila, but that progerin causes a stronger phenotype than wild-type lamin A.

A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence

2021 ◽  
Vol 13 (575) ◽  
pp. eabd2655
Author(s):  
Wei Wang ◽  
Yuxuan Zheng ◽  
Shuhui Sun ◽  
Wei Li ◽  
Moshi Song ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Werner Syndrome ◽  
Embryonic Stem ◽  
Accelerated Aging ◽  
Premature Aging ◽  
Mesenchymal Precursor Cells ◽  
Genome Wide ◽  
A Genome ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Understanding the genetic and epigenetic bases of cellular senescence is instrumental in developing interventions to slow aging. We performed genome-wide CRISPR-Cas9–based screens using two types of human mesenchymal precursor cells (hMPCs) exhibiting accelerated senescence. The hMPCs were derived from human embryonic stem cells carrying the pathogenic mutations that cause the accelerated aging diseases Werner syndrome and Hutchinson-Gilford progeria syndrome. Genes whose deficiency alleviated cellular senescence were identified, including KAT7, a histone acetyltransferase, which ranked as a top hit in both progeroid hMPC models. Inactivation of KAT7 decreased histone H3 lysine 14 acetylation, repressed p15INK4b transcription, and alleviated hMPC senescence. Moreover, lentiviral vectors encoding Cas9/sg-Kat7, given intravenously, alleviated hepatocyte senescence and liver aging and extended life span in physiologically aged mice as well as progeroid Zmpste24−/− mice that exhibit a premature aging phenotype. CRISPR-Cas9–based genetic screening is a robust method for systematically uncovering senescence genes such as KAT7, which may represent a therapeutic target for developing aging interventions.

Familial Turner syndrome: the importance of information

2016 ◽  
Vol 29 (5) ◽  
Author(s):  
Isabel Periquito ◽  
Catarina Carrusca ◽  
Joana Morgado ◽  
Brígida Robalo ◽  
Carla Pereira ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Unusual Case ◽  
Growth Hormone Treatment ◽  
Genetic Disorder ◽  
Hormone Treatment ◽  
Live Births ◽  
Tertiary Center ◽  
Common Genetic Disorder

AbstractTurner syndrome is a common genetic disorder with an incidence of 1 in 2500 live births. Spontaneous fertility is rare in such patients and is most likely in women with mosaicism or very distal Xp deletions. The authors report an unusual case of familial Turner syndrome in a woman with mosaicism 45,X/46,Xdel(Xp) karyotype with three documented spontaneous pregnancies, which resulted in two daughters with 46,Xdel(X)(p11.4)mat karyotype and a healthy son. The mother was first diagnosed by the age of 11 and did not receive contraceptive medication, due to information that she would be infertile. Both daughters were referred to an endocrinology unit and are now under growth hormone treatment, and have been growing in the 3rd percentile. This family illustrates the complexity and difficulties in counseling, follow-up and treatment in Turner syndrome, namely referring to a tertiary center, fertility and treatment such as growth hormone and hormonal replacement, due to the heterogeneity of the clinical spectrum.

scholarly journals Hutchinson-Gilford Progeria Syndrome in a Young Man

2018 ◽  
Vol 5 (4) ◽  
pp. 3727-3728
Author(s):  
Maryam. Moinazad Tehrani MD ◽  
Agin Khosrow MD
Keyword(s):  
Genetic Disorder ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Artery Bypass Graft ◽  
Average Life ◽  
Average Life Expectancy ◽  
Atrial Septum Defect ◽  
Asd Closure ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder. It shows a characteristic progeria phenotype. The average life expectancy of HGPS patients is reported to be  ~ 14.6 years. A case was a 33-year-old man with progeria phenotype, severe cardiac failure, and convulsion. He had several cardiac surgeries include Mitral and Aortic valve replacement, Atrial Septum Defect (ASD) closure and Coronary Artery Bypass Graft (CABG) .

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