Description:
HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
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 |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Ethnicity
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MEXICAN
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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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ISCN
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46,XY
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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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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed 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 |
Donor has classical features of progeria, but no signs of heart disease. Parents and sibs are clinically unaffected. The culture was initiated on 5/16/79 by transformation of lymphocytes with Epstein Barr virus. The cells grow in suspension and their morphology is spherical. The karyotype is 46,XY; normal diploid male. Blood specimen was obtained ante-mortem. A skin fibroblast culture from same donor is AG03513D. 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. |
| Bracci AN, Dallmann A, Ding Q, Hubisz MJ, Caballero M, Koren A, The evolution of the human DNA replication timing program Proceedings of the National Academy of Sciences of the United States of America120:e2213896120 2023 |
| PubMed ID: 36848554 |
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| Caballero M, Ge T, Rebelo AR, Seo S, Kim S, Brooks K, Zuccaro M, Kanagaraj R, Vershkov D, Kim D, Smogorzewska A, Smolka M, Benvenisty N, West SC, Egli D, Mace EM, Koren A, Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation Human molecular genetics120:e2213896120 2021 |
| PubMed ID: 35394024 |
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| Scaffidi P, Misteli T, Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med11(4):440-5 2005 |
| PubMed ID: 15750600 |
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| Cao H, Hegele RA, LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet48(5):271-4 2003 |
| PubMed ID: 12768443 |
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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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