1. Progeria 101: Frequently Asked Questions
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De Barsy Syndrome: Orthopedic Case Report and Literature Review
MOJ Orthopedics & Rheumatology De Barsy Syndrome: Orthopedic Case report and Literature Review Introduction Case Report Volume 7 Issue 5 - 2017 This condition was first described in 1968 by De Barsy who and degeneration of the elastic tissue of the cornea and skin, Jose de Jesus Guerra Jasso1*, Douglas reported a case of a patient with progeria, dwarfism, oligofrenia and since then, it is known as Barsy Syndrome or Barsy- Colmenares Bonilla2 and Loreett Ocampo Perez3 of progeroid aspect, cutis laxa, corneal opacity, intrauterine 1Pediatric Orthopedics, Hospital Regional de Alta Especialidad growthMoens-Dierckx retardation Syndrome. and severe This ismental defined retardation as the combination (although del Bajio, Mexico some will learn to speak, intelligence is less than normal) [1]. 2Pediatric Orthopedic Service, Hospital regional de alta especialidad del bajio The orthopedic manifestations are dysplasia of hip development, 3Fellow of Pediatric Orthopedics, Hospital Regional de Alta hyper laxity of severe joints, athetoid movements, scoliosis and Especialidad del Bajio, Mexico severe deformities of the foot. Epidemiology in Latin America is unknown because of its underdiagnosis and when confused *Corresponding author: Jesus Guerra Jasso, Hospital with other connective tissue pathologies (Hutchinson-Gilford Regional de Alta Especialidad del Bajio, Boulevard Milenio No. 130. Col, San Carlos la Roncha, C.P. 37660, Guanajuato, syndrome, gerodermic osteodiplasia, even Ehlers-Danlos), the Mexico, Tel: 477-267 2000; Ext-1403; life expectancy of these patients varies according to the degree of Email: penetrance and in the world literature, there are very few reports (about 50), so the diagnosis requires a challenge [2]. Received: January 13, 2017 | Published: March 21, 2017 Clinical Case and thick clamp. -
DNA Damage in the Oligodendrocyte Lineage and Its Role in Brain Aging
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Mech Ageing Manuscript Author Dev. Author Manuscript Author manuscript; available in PMC 2018 January 01. Published in final edited form as: Mech Ageing Dev. 2017 January ; 161(Pt A): 37–50. doi:10.1016/j.mad.2016.05.006. DNA damage in the oligodendrocyte lineage and its role in brain aging Kai-Hei Tse1,2 and Karl Herrup1 1 Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong Abstract Myelination is a recent evolutionary addition that significantly enhances the speed of transmission in the neural network. Even slight defects in myelin integrity impair performance and enhance the risk of neurological disorders. Indeed, myelin degeneration is an early and well-recognized neuropathology that is age associated, but appears before cognitive decline. Myelin is only formed by fully differentiated oligodendrocytes, but the entire oligodendrocyte lineage are clear targets of the altered chemistry of the aging brain. As in neurons, unrepaired DNA damage accumulates in the postmitotic oligodendrocyte genome during normal aging, and indeed may be one of the upstream causes of cellular aging - a fact well illustrated by myelin co-morbidity in premature aging syndromes arising from deficits in DNA repair enzymes. The clinical and experimental evidence from Alzheimer's disease, progeroid syndromes, ataxia-telangiectasia and other conditions strongly suggest that oligodendrocytes may in fact be uniquely vulnerable to oxidative DNA damage. If this damage remains unrepaired, as is increasingly true in the aging brain, myelin gene transcription and oligodendrocyte differentiation is impaired. Delineating the relationships between early myelin loss and DNA damage in brain aging will offer an additional dimension outside the neurocentric view of neurodegenerative disease. -
The Progeria Syndrome Fact Sheet
HUTCHINSON-GILFORD PROGERIA SYNDROME FREQUENTLY ASKED QUESTIONS WHAT IS PROGERIA? Hutchinson-Gilford Progeria Syndrome “Progeria” or “HGPS” is a rare, fatal genetic condition characterized by an appearance of accelerated aging in children. Its name is derived from the Greek and means "prematurely old." While there are different forms of Progeria*, the classic type is Hutchinson- Gilford Progeria Syndrome, which was named after the doctors who first described it in England: in 1886 by Dr. Jonathan Hutchinson, and in 1897 by Dr. Hastings Gilford. HOW COMMON IS PROGERIA? Progeria affects approximately 1 in 4 - 8 million newborns. It affects both sexes equally and all races. In the past 15 years, children with Progeria have been reported all over the world , including in: Algeria Cuba Ireland Peru Sweden Argentina Denmark Israel Philippines Switzerland Australia Dominican Italy Poland Turkey Austria Republic Japan Portugal United States Belgium Egypt Libya Puerto Rico Venezuela Brazil England Mexico Romania Vietnam Canada France Morocco South Africa Yugoslavia China Germany Netherlands South Korea Columbia India Pakistan Spain WHAT ARE THE FEATURES OF PROGERIA? Although they are born looking healthy, most children with Progeria begin to display many characteristics of Progeria within the first year of life. Progeria signs include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular (heart) disease and stroke. The children have a remarkably similar appearance, despite differing ethnic backgrounds. Children with Progeria die of atherosclerosis (heart disease) at an average age of thirteen years (with a range of about 8 – 21 years). WHAT DOES PROGERIA HAVE TO DO WITH AGING? Children with Progeria are genetically predisposed to premature, progressive heart disease. -
Progerinin, an Optimized Progerin-Lamin a Binding Inhibitor
ARTICLE https://doi.org/10.1038/s42003-020-01540-w OPEN Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome 1234567890():,; So-mi Kang1,7, Min-Ho Yoon1,7, Jinsook Ahn2, Ji-Eun Kim3, So Young Kim4, Seock Yong Kang4, Jeongmin Joo4, Soyoung Park1, Jung-Hyun Cho1, Tae-Gyun Woo1, Ah-Young Oh1, Kyu Jin Chung3, So Yon An5, ✉ Tae Sung Hwang5, Soo Yong Lee6, Jeong-Su Kim6, Nam-Chul Ha2, Gyu-Yong Song3 & Bum-Joon Park 1 Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient’s cells, and very short life span in an in vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated in in vivo pharmaco- kinetic (PK) analysis. Thus, we improved its property through chemical modification and obtained an optimized drug candidate, Progerinin (SLC-D011). This chemical can extend the life span of LmnaG609G/G609G mouse for about 10 weeks and increase its body weight. Progerinin can also extend the life span of LmnaG609G/+ mouse for about 14 weeks via oral administration, whereas treatment with lonafarnib (farnesyl-transferase inhibitor) can only extend the life span of LmnaG609G/+ mouse for about two weeks. In addition, progerinin can induce histological and physiological improvement in LmnaG609G/+ mouse. These results indicate that progerinin is a strong drug candidate for HGPS. 1 Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, Korea. 2 Department of Food Science, College of Agricultural Science, Seoul National University, Seoul, Korea. -
Alterations in Mitosis and Cell Cycle Progression Caused by a Mutant Lamin a Known to Accelerate Human Aging
Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging Thomas Dechat*, Takeshi Shimi*, Stephen A. Adam*, Antonio E. Rusinol†, Douglas A. Andres‡, H. Peter Spielmann‡§¶, Michael S. Sinensky†, and Robert D. Goldman*ʈ *Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611; †Department of Biochemistry and Molecular Biology, James H. Quillen College of Medicine, East Tennessee State University, Box 70581, Johnson City, TN 37614; and Departments of ‡Molecular and Cellular Biochemistry and §Chemistry and ¶Kentucky Center for Structural Biology, University of Kentucky, 741 South Limestone, Lexington, KY 40536 Communicated by Francis S. Collins, National Institutes of Health, Bethesda, MD, February 2, 2007 (received for review December 19, 2006) Mutations in the gene encoding nuclear lamin A (LA) cause the DNA repair defects, changes in histone methylation, and loss of premature aging disease Hutchinson–Gilford Progeria Syndrome. heterochromatin (5, 17–19). However, the impact of LA⌬50/ The most common of these mutations results in the expression of progerin on mitosis and its consequences for daughter cells a mutant LA, with a 50-aa deletion within its C terminus. In this entering G1 have not been determined. An initial insight into study, we demonstrate that this deletion leads to a stable farne- changes in early G1 came from studies of HeLa cells expressing sylation and carboxymethylation of the mutant LA (LA⌬50/prog- GFP-LA⌬50/progerin, in which this mutant protein is abnor- erin). These modifications cause an abnormal association of LA⌬50/ mally retained in cytoplasmic structures after nuclear assembly progerin with membranes during mitosis, which delays the onset is completed (5). -
Atypical Progeroid Syndrome ID: 20-0188; April 2021 (P.E262K LMNA) DOI: 10.1530/EDM-20-0188
ID: 20-0188 -20-0188 M Yukina and others Atypical progeroid syndrome ID: 20-0188; April 2021 (p.E262K LMNA) DOI: 10.1530/EDM-20-0188 Atypical progeroid syndrome (p.E262K LMNA mutation): a rare cause of short stature and osteoporosis Correspondence Marina Yukina, Nurana Nuralieva, Ekaterina Sorkina, Ekaterina Troshina, should be addressed Anatoly Tiulpakov, Zhanna Belaya and Galina Melnichenko to E Sorkina Email Endocrinology Research Centre, Moscow, Russia [email protected] Summary Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson–Gilford progeria syndrome, mandibuloacral dysplasia, atypical progeroid syndrome (APS) and generalized lipodystrophy- associated progeroid syndrome (GLPS). All of those syndromes are associated with some progeroid features, lipodystrophyandmetaboliccomplicationsbutvarydifferentlydependingonaparticularmutationandevenpatients carrying the same gene variant are known to have clinical heterogeneity. We report a new 30-year-old female patient from Russia with an APS and generalized lipodystrophy (GL) due to the heterozygous de novo LMNA p.E262K mutation and compare her clinical and metabolic features to those of other described patients with APS. Despite many health issues, short stature, skeletal problems, GL and late diagnosis of APS, our patient seems to be relatively metabolically healthy for her age when compared to previously described patients with APS. Learning points: • Atypicalprogeroidsyndromes(APS)arerareandheterogenicwithdifferentageofonsetanddegreeofmetabolic -
Neurodegeneration in Accelerated Aging
DOCTOR OF MEDICAL SCIENCE DANISH MEDICAL JOURNAL Neurodegeneration in Accelerated Aging Morten Scheibye-Knudsen This review has been accepted as a thesis together with 7 previously published pa- pers by the University of Copenhagen, October 16, 2014 and defended on January 14, 2016 Official opponents: Alexander Bürkle, University of Konstanz Lars Eide, University of Oslo Correspondence: Center for Healthy Aging, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen E-mail: [email protected] Dan Med J 2016;63(11):B5308 INTRODUCTION The global elderly population has been progressively increasing throughout the 20th century and this growth is projected to per- sist into the late 21st century resulting in 20% of the total world population being aged 65 or more by the year 2100 (Figure 1). 80% of the total cost of health care is accrued after 40 years of Figure 2. The phenotype of human aging. age where chronic diseases become prevalent [1, 2]. With an ex- that appear to regulate the aging process [4,5]. These include the ponential increase in health care costs, it follows that the chronic insulin and IGF-1 signaling cascades [4], protein synthesis and diseases that accumulate in an aging population poses a serious quality control [6], regulation of cell proliferation through factors socioeconomic problem. Finding treatments to age related dis- such as mTOR [7], stem cell maintenance 8 as well as mitochon- eases, therefore becomes increasingly more pertinent as the pop- drial preservation [9]. Most of these pathways are conserved ulation ages. Even more so since there appears to be a continu- through evolution and appear to regulate aging in many lower or- ous increase in the prevalence of chronic diseases in the aging ganisms. -
Trichothiodystrophy
Trichothiodystrophy Author: Doctor Alfredo Rossi1 and Doctor C. Cantisani. Creation date: June 2004 Scientific Editor: Prof Antonella Tosti 1Dipartimento di Malattie Cutanee-Veneree Chirurgia Plastica-Ricostruttiva, Università degli studi di Roma “La Sapienza” Abstract Keywords Definition Epidemiology Etiology Clinical description Diagnostic methods Prenatal diagnosis Management References Abstract Trichothiodystrophy (TTD) is a rare autosomal recessive genetic disorder characterized by abnormal synthesis of the sulphur containing keratins and consequently hair dysplasia, associated with numerous symptoms affecting mainly organs derived from the neuroectoderm. This phenotypic aspect is due to mutations in the DNA-dependent ATPase/helicase subunit of TFIIH, XPB and XPD. Abnormalities in excision repair of ultraviolet (UV)-damaged DNA are recognized in about half of the patients. The clinical appearance is characterized by brittle and fragile hair, congenital ichthyosis, nail and dental dysplasias, cataract, progeria-like face, growth and mental retardation. The abnormalities are usually obvious at birth, with variable clinical expression. The variants of TTD, depending on their different associations, are known by the initials BIDS, IBIDS, PIBIDS, SIBIDS, ONMRS, as well as the eponyms of the Pollit, Tay, Sabinas syndromes or Amish brittle hair. The exact prevalence of TTD is unknown, but appears to be rather uncommon. About 20 cases of PIBI(D)S have been reported in the literature. Up to 1991, clinical data of 15 cases with IBIDS were published. Prenatal diagnostic of TTD is available. There is no specific treatment. Keywords Brittle hair, photosensitivity, ichthyosis, BIDS, IBIDS, PIBIDS, SIBIDS, ONMRS, Tay-syndrome Definition tail pattern). They named it Trichothiodystrophy, Trichothiodystrophy (TTD) is a group of rare noticing also an increased Photosensitivity and autosomal recessive disorders with heterogenic Ichthyosis in these patients (PIBIDS). -
Molecular Basis of Progeroid Syndromes–S–S– the Wwthe Erner Andanderner Hutchinson-Gilford Syndromes
Proc. Indian natn Sci Acad. B69 No. 4 pp 625-640 (2003) Molecular Basis of Progeroid Syndromes–s–s– the WWthe erner andanderner Hutchinson-Gilford Syndromes JUNKO OSHIMA*, NANCY B HANSON and GEORGE M MARTIN Department of Pathology, University of W ashington, Seattle, WA 98195, USA (Received on 17 July 2003; Accepted after r evision on 6 August 2003) Segmental progeroid syndromes are members of a group of disorders in which affected individuals present various featur es suggestive of accelerated aging. The two best-known examples are the Werner syndro m e (WS; “Progeria of the adult”) and the Hutchinson-Gilford Progeria syndrome (HGPS; “Progeria of child- hood”). The gene responsible for WS, WRN, was identified in 1996 and encodes a multifunctional nuclear protein with exonuclease and helicase domains. WS patients and cells isolated from the WS patients show various genomic instability phenotypes, including an incr eased incidence of cancer. The WRN protein is thought to play a crucial role in optimizing the regulation of DNA repair processes. Recently, a novel r ecurr ent mutation in the LMNA gene has been shown to be responsible for HGPS. LMNA encodes nuclear intermediate filaments, lamins A and C; mutant lamins are thought to result in nuclear fragility. Ther e ar e at least six other disor ders caused by LMNA mutations, most of which affect cells and tissues of mesenchymal origins, including atypical forms of WS. The pathophysiologies of these and certain other progeroid syndromes indicate an important role for DNA damage in the genesis of common age- related disorders. Key WWKey ords: WWords: erner syndrome, WRN, RecQ, Hutchinson-Gilford Progeria syndrome, LMNA, Lamin, Genomic instability, Aging, Human Introduction of WS, previously based upon clinical criteria, can Segmental progeroid syndromes encompass a now be confirmed by molecular biological methods. -
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2018, 65 (2), 227-238 Note Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene Haruka Sasaki1), 2), Kumiko Yanagi3) *, Satoshi Ugi4), Kunihisa Kobayashi1), Kumiko Ohkubo5), Yuji Tajiri6), Hiroshi Maegawa4), Atsunori Kashiwagi7) and Tadashi Kaname3) * 1) Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka 818-8502, Japan 2) Division of Diabetic Medicine, Bunyukai Hara Hospital, Ohnojo, Fukuoka 816-0943, Japan 3) Department of Genome Medicine, National Research Institute for Child Health, Setagaya, Tokyo 157-8535, Japan 4) Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan 5) Department of Laboratory Medicine, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan 6) Division of Endocrinology and Metabolism, Kurume University School of Medicine, Kurume, Fukuoka 830-0111, Japan 7) Diabetes Center, Seikokai Kusatsu General Hospital, Kusatsu, Shiga 525-8585, Japan Abstract. Segmental progeroid syndromes with lipodystrophy are extremely rare, heterogeneous, and complex multi-system disorders that are characterized by phenotypic features of premature aging affecting various tissues and organs. In this study, we present a “sporadic/isolated” Japanese woman who was ultimately diagnosed with mandibular hypoplasia, deafness, progeroid features, and progressive lipodystrophy (MDPL) syndrome (MIM #615381) using whole exome sequencing analysis. She had been suspected as having atypical Werner syndrome and/or progeroid syndrome based on observations spanning a 30-year period; however, repeated genetic testing by Sanger sequencing did not identify any causative mutation related to various subtypes of congenital partial lipodystrophy (CPLD) and/or mandibular dysplasia with lipodystrophy (MAD). -
Human Radiosensitivity and Radiosusceptibility: What Are the Differences?
International Journal of Molecular Sciences Review Human Radiosensitivity and Radiosusceptibility: What Are the Differences? Laura El-Nachef 1, Joelle Al-Choboq 1, Juliette Restier-Verlet 1, Adeline Granzotto 1, Elise Berthel 1,2, Laurène Sonzogni 1,Mélanie L. Ferlazzo 1, Audrey Bouchet 1 , Pierre Leblond 3, Patrick Combemale 3, Stéphane Pinson 4, Michel Bourguignon 1,5 and Nicolas Foray 1,* 1 Inserm, U1296 unit, Radiation: Defense, Health and Environment, Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France; [email protected] (L.E.-N.); [email protected] (J.A.-C.); Juliette.Restier–[email protected] (J.R.-V.); [email protected] (A.G.); [email protected] (E.B.); [email protected] (L.S.); [email protected] (M.L.F.); [email protected] (A.B.); [email protected] (M.B.) 2 Neolys Diagnostics, 67960 Entzheim, France 3 Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon, France; [email protected] (P.L.); [email protected] (P.C.) 4 Hospices Civils de Lyon, Quai des Célestins, 69002 Lyon, France; [email protected] 5 Université Paris Saclay Versailles St Quentin en Yvelines, 78035 Versailles, France * Correspondence: [email protected]; Tel.: +33-4-78-78-28-28 Abstract: The individual response to ionizing radiation (IR) raises a number of medical, scientific, and societal issues. While the term “radiosensitivity” was used by the pioneers at the beginning Citation: El-Nachef, L.; Al-Choboq, of the 20st century to describe only the radiation-induced adverse tissue reactions related to cell J.; Restier-Verlet, J.; Granzotto, A.; death, a confusion emerged in the literature from the 1930s, as “radiosensitivity” was indifferently Berthel, E.; Sonzogni, L.; Ferlazzo, used to describe the toxic, cancerous, or aging effect of IR. -
Expression of Progerin Does Not Result in an Increased Mutation Rate
bioRxiv preprint doi: https://doi.org/10.1101/047506; this version posted April 6, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Expression of progerin does not result in an increased mutation rate. Emmanuelle Deniaud1, Shelagh Boyle1 and Wendy A. Bickmore1* 1 MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK *Correspondence to: Wendy Bickmore, MRC Human Genetics Unit, IGMM, Crewe Road, Edinburgh EH4 2XU, UK Email:[email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/047506; this version posted April 6, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract In the premature ageing disease Hutchinson-Gilford progeria syndrome (HGPS) the underlying genetic defect in the lamin A gene leads to accumulation at the nuclear lamina of progerin – a mutant form of lamin A that cannot be correctly processed. This has been reported to result in defects in the DNA damage response and in DNA repair, leading to the hypothesis that, as in normal ageing and in other progeroid syndromes caused by mutation of genes of the DNA repair and DNA damage response pathways, increased DNA damage may be responsible for the premature ageing phenotypes in HGPS patients.