NG06297
DNA from Fibroblast
Description:
HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
LAMIN A/C; LMNA
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Repository
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NIA Aging Cell Culture Repository
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| Subcollection |
Heritable Diseases |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Thigh
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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White
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
4.45 |
| Passage Frozen |
18 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis and by Chromosome Analysis |
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| Gene |
LMNA |
| Chromosomal Location |
1q21.2 |
| Allelic Variant 1 |
150330.0022; HUTCHINSON-GILFORD PROGERIA SYNDROME |
| Identified Mutation |
GLY608GLY; Description: In 18 of 20 patients with classic Hutchinson-Gilford progeria syndrome (176670), Eriksson et al. [Nature 423: 293 (2003)] found an identical de novo single-base substitution, a C-to-T change resulting in a silent gly-to-gly mutation at codon 608 (G608G) within exon 11 of the LMNA gene. This substitution created an exonic consensus splice donor sequence and resulted in activation of a cryptic splice site and deletion of 50 basepairs of prelamin A. This mutation was not identified in any of the 16 parents available for testing. |
| Remarks |
The donor had classic features of progeria and died at age 14 years of congestive heart failure. Autopsy revealed severe coronary-vascular disease. The biopsy was taken ante-mortem on 1/11/72 from skin on the anterior thigh region. The culture was initiated using explants of minced skin tissue. The cell morphology is fibroblast-like. The karyotype is 46,XY; normal diploid male. Culture is frozen at PDL 33 and has a maximum lifespan of 40 PD. Donor subject has a de novo single base substitution, a C>T change at nucleotide 2036 (2036C>T), which results in a silent change at codon 608 [Gly608Gly (G608G)] in exon 11 of the Lamin A gene (LMNA). This substitution creates an exonic consensus splice donor sequence and results in activation of a cryptic splice site which in turn causes skipping of 150 bp of the LMNA mRNA leading to the deletion of 50 amino acids from the protein. This altered LMNA protein was detected on western blots [Eriksson et al., Nature 423:293 (2003)]. The legacy karyotype description shown in this Remark may not be representative of the current available product. |
| Della Valle F, Reddy P, Yamamoto M, Liu P, Saera-Vila A, Bensaddek D, Zhang H, Prieto Martinez J, Abassi L, Celii M, Ocampo A, Nuñez Delicado E, Mangiavacchi A, Aiese Cigliano R, Rodriguez Esteban C, Horvath S, Izpisua Belmonte JC, Orlando V, LINE-1 RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes Science translational medicine14:eabl6057 2022 |
| PubMed ID: 35947677 |
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| Kychygina A, Dall'Osto M, Allen JAM, Cadoret JC, Piras V, Pickett HA, Crabbe L, Progerin impairs 3D genome organization and induces fragile telomeres by limiting the dNTP pools Scientific reports11:13195 2021 |
| PubMed ID: 34162976 |
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| Lee J, Bignone PA, Coles LS, Liu Y, Snyder E, Larocca D, Induced pluripotency and spontaneous reversal of cellular aging in supercentenarian donor cells Biochemical and biophysical research communications11:13195 2020 |
| PubMed ID: 32115145 |
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| Puttaraju M, Jackson M, Klein S, Shilo A, Bennett CF, Gordon L, Rigo F, Misteli T, Systematic screening identifies therapeutic antisense oligonucleotides for Hutchinson-Gilford progeria syndrome Nature medicine27:526-535 2020 |
| PubMed ID: 33707772 |
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| Fan JR, You LR, Wang WJ, Huang WS, Chu CT, Chi YH, Chen HC, Lamin A-mediated nuclear lamina integrity is required for proper ciliogenesis EMBO reports27:e49680 2019 |
| PubMed ID: 32815283 |
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| Hamczyk MR, Villa-Bellosta R, Quesada V, Gonzalo P, Vidak S, Nevado RM, Andrés-Manzano MJ, Misteli T, López-Otín C, Andrés V, Progerin accelerates atherosclerosis by inducing endoplasmic reticulum stress in vascular smooth muscle cells EMBO molecular medicine11:e49680 2019 |
| PubMed ID: 30862662 |
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| Bikkul MU1, Faragher RGA2, Worthington G1, Meinke P3,4, Kerr ARW4, Sammy A1, Riyahi K1, Horton D1, Schirmer EC4, Hubank M5, Kill IR1, Anderson RM1, Slijepcevic P1, Makarov E1, Bridger JM1., Telomere elongation through hTERT immortalisation leads to chromosome repositioning in control cells and genomic instability in Hutchinson-Gilford Progeria syndrome fibroblasts, expressing a novel SUN1 isoform Genes Chromosomes Cancer11:e49680 2018 |
| PubMed ID: 30474255 |
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| Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B, Tu EY, Mandal PK, Vera E, Shim JW, Kriks S, Taldone T, Fusaki N, Tomishima MJ, Krainc D, Milner TA, Rossi DJ, Studer L., Human iPSC-Based Modeling of Late-Onset Disease via Progerin-Induced Aging. Cell Stem Cell.13(6):691-705 2013 |
| PubMed ID: 24315443 |
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| Rivera-Torres J, Acín-Perez R, Cabezas-Sánchez P, Osorio FG, Gonzalez-Gómez C, Megias D, Cámara C, López-Otín C, Enríquez JA, Luque-García JL, Andrés V., Identification of mitochondrial dysfunction in Hutchinson-Gilford progeria syndrome through use of stable isotope labeling with amino acids in cell culture. J Proteomics.91C:466-477 2013 |
| PubMed ID: 23969228 |
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| Chen CY, Chi YH, Mutalif RA, Starost MF, Myers TG, Anderson SA, Stewart CL, Jeang KT., Accumulation of inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies. Cell149:565-77 2012 |
| PubMed ID: 22541428 |
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| Zhang J, Lian Q, Zhu G, Zhou F, Sui L, Tan C, Mutalif RA, Navasankari R, Zhang Y, Tse HF, Stewart CL, Colman A, A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects Cell stem cell8:31-45 2010 |
| PubMed ID: 21185252 |
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| Britt-Compton B, Wyllie F, Rowson J, Capper R, Jones RE, Baird DM, Telomere dynamics during replicative senescence are not directly modulated by conditions of oxidative stress in IMR90 fibroblast cells Biogerontology8:31-45 2008 |
| PubMed ID: 19214769 |
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| Decker ML, Chavez E, Vulto I, Lansdorp PM, Telomere length in Hutchinson-Gilford progeria syndrome Mechanisms of ageing and development130:377-83 2008 |
| PubMed ID: 19428457 |
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| Moulson CL, Fong LG, Gardner JM, Farber EA, Go G, Passariello A, Grange DK, Young SG, Miner JH, Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes Human mutation28:882-9 2007 |
| PubMed ID: 17469202 |
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| Scaffidi P, Misteli T, Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing Nature cell biology28:882-9 2007 |
| PubMed ID: 18311132 |
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| Glynn MW, Glover TW, Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition Human molecular genetics14:2959-69 2005 |
| PubMed ID: 16126733 |
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| Bridger JM, Kill IR, Aging of Hutchinson-Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis. Exp Gerontol39(5):717-24 2004 |
| PubMed ID: 15130666 |
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| Wallis CV, Sheerin AN, Green MH, Jones CJ, Kipling D, Faragher RG, Fibroblast clones from patients with Hutchinson-Gilford progeria can senesce despite the presence of telomerase. Exp Gerontol39(4):461-7 2004 |
| PubMed ID: 15050279 |
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| Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS, Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature423(6937):293-8 2003 |
| PubMed ID: 12714972 |
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| Ly DH, Lockhart DJ, Lerner RA, Schultz PG, Mitotic misregulation and human aging. Science287(5462):2486-92 2000 |
| PubMed ID: 10741968 |
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| Winkles JA, O'Connor ML, Friesel R, Altered regulation of platelet-derived growth factor A-chain and c-fos gene expression in senescent progeria fibroblasts. J Cell Physiol144:313-25 1990 |
| PubMed ID: 2166059 |
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| Goldstein S, Moerman E, Heat-labile enzymes in skin fibroblasts from subjects with progeria. N Engl J Med292:1305-9 1975 |
| PubMed ID: 1128606 |
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