NG04110
DNA from Fibroblast
Description:
WERNER SYNDROME; WRN REPLICATION FOCUS-FORMING ACTIVITY 1, INCLUDED; FFA1, INCLUDED
LAMIN A/C; LMNA
NIA AGING CELL REPOSITORY DNA PANEL - AGING SYNDROMES
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Repository
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NIA Aging Cell Culture Repository
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| Subcollection |
Heritable Diseases |
| Quantity |
10ug |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Skin
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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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Family Member
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1
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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 |
4.12 |
| Passage Frozen |
9 |
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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 |
E578V; WERNER SYNDROME |
| Identified Mutation |
GLU578VAL |
| Remarks |
The sample was originally submitted with an uncertain diagnosis of either severe Werner syndrome or mild Progeria. Additional information that was made available suggested that the patient should be classified as Werner syndrome with the comment that the distinction was arbitrary without a biochemical test. The sample was obtained when the child was 13 yr old. She had short stature and dysmorphic features. Physical examination showed large coarse brown freckles over the entire body, thin skin on hands and feet, clinodactyly of 4th and 5th digits of each hand and 4th digit of the right foot, bilateral simian creases and decreased flexion of fingers bilaterally. Chromosome examination was normal. Impression was of accelerated aging. Height was 137.2 cm (<5th percentile), Wt 26 kg (<5th percentile) and head circumference 51.1 cm (<2nd percentile). Dentition was poor, and spine had scoliosis. She has the atrophic skin changes, short stature, beak nose and high-pitched voice common to both progeria and Werner syndrome. Family history was unremarkable. This donor is heterozygous for an A-to-T substitution at nucleotide 1945 (1945A>T) in exon 11 of the LMNA gene, resulting in a missense mutation in codon 578 [GLU578VAL (E578V)]. |
| 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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| Toth JI, Yang SH, Qiao X, Beigneux AP, Gelb MH, Moulson CL, Miner JH, Young SG, Fong LG, Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes Proceedings of the National Academy of Sciences of the United States of America102:12873-8 2005 |
| PubMed ID: 16129834 |
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| Csoka AB, Cao H, Sammak PJ, Constantinescu D, Schatten GP, Hegele RA, Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes. J Med Genet41(4):304-8 2004 |
| PubMed ID: 15060110 |
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| Blander G, Zalle N, Leal JF, Bar-Or RL, Yu CE, Oren M, The Werner syndrome protein contributes to induction of p53 by DNA damage. FASEB J14(14):2138-40 2000 |
| PubMed ID: 11023999 |
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| Marciniak RA, Lombard DB, Johnson FB, Guarente L, Nucleolar localization of the Werner syndrome protein in human cells. Proc Natl Acad Sci U S A95(12):6887-92 1998 |
| PubMed ID: 9618508 |
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