Truncated prelamin A expression in HGPS-like patients: A transcriptional study

Florian Barthélémy, Claire Navarro, Racha Fayek, Nathalie Da Silva, Patrice Roll, Sabine Sigaudy, Junko Oshima, Gisèle Bonne, Kyriaki Papadopoulou-Legbelou, Athanasios E. Evangeliou, Martha Spilioti, Martine Lemerrer, Ron A. Wevers, Eva Morava-Kozicz, Andrée Robaglia-Schlupp, Nicolas Lévy, Marc Bartoli, Annachiara De Sandre-Giovannoli

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Premature aging syndromes are rare genetic disorders mimicking clinical and molecular features of aging. A recently identified group of premature aging syndromes is linked to mutation of the LMNA gene encoding lamins A and C, and is associated with nuclear deformation and dysfunction. Hutchinson-Gilford progeria syndrome (HGPS) was the first premature aging syndrome linked to LMNA mutation and its molecular bases have been deeply investigated. It is due to a recurrent de novo mutation leading to aberrant splicing and the production of a truncated and toxic nuclear lamin A precursor (prelamin AΔ50), also called progerin. In this work and based on the literature data, we propose to distinguish two main groups of premature aging laminopathies: (1) HGPS and HGP-like syndromes, which share clinical features due to hampered processing and intranuclear toxic accumulation of prelamin A isoforms; and (2) APS (atypical progeria syndromes), due to dominant or recessive missense mutations affecting lamins A and C. Among HGPS-like patients, several deleted prelamin A transcripts (prelamin AΔ50, AΔ35 and AΔ90) have been described. The purpose of this work was to characterize those transcripts in eight patients affected with HGP-like rare syndromes. When fibroblasts were available, the relationships between the presence and ratios of these transcripts and other parameters were studied, aiming to increase our understanding of genotype-phenotype relationships in HGPS-like patients. Altogether our results evidence that progerin accumulation is the major pathogenetic mechanism responsible for HGP-like syndromes due to mutations near the donor splice site of exon 11.

Original languageEnglish (US)
Pages (from-to)1051-1061
Number of pages11
JournalEuropean Journal of Human Genetics
Volume23
Issue number8
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Progeria
Premature Aging
Lamin Type A
Mutation
Poisons
RNA Splice Sites
Inborn Genetic Diseases
Missense Mutation
prelamin A
Exons
Protein Isoforms
Fibroblasts
Genotype
Phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Barthélémy, F., Navarro, C., Fayek, R., Da Silva, N., Roll, P., Sigaudy, S., ... De Sandre-Giovannoli, A. (2015). Truncated prelamin A expression in HGPS-like patients: A transcriptional study. European Journal of Human Genetics, 23(8), 1051-1061. https://doi.org/10.1038/ejhg.2014.239

Truncated prelamin A expression in HGPS-like patients : A transcriptional study. / Barthélémy, Florian; Navarro, Claire; Fayek, Racha; Da Silva, Nathalie; Roll, Patrice; Sigaudy, Sabine; Oshima, Junko; Bonne, Gisèle; Papadopoulou-Legbelou, Kyriaki; Evangeliou, Athanasios E.; Spilioti, Martha; Lemerrer, Martine; Wevers, Ron A.; Morava-Kozicz, Eva; Robaglia-Schlupp, Andrée; Lévy, Nicolas; Bartoli, Marc; De Sandre-Giovannoli, Annachiara.

In: European Journal of Human Genetics, Vol. 23, No. 8, 01.01.2015, p. 1051-1061.

Research output: Contribution to journalArticle

Barthélémy, F, Navarro, C, Fayek, R, Da Silva, N, Roll, P, Sigaudy, S, Oshima, J, Bonne, G, Papadopoulou-Legbelou, K, Evangeliou, AE, Spilioti, M, Lemerrer, M, Wevers, RA, Morava-Kozicz, E, Robaglia-Schlupp, A, Lévy, N, Bartoli, M & De Sandre-Giovannoli, A 2015, 'Truncated prelamin A expression in HGPS-like patients: A transcriptional study', European Journal of Human Genetics, vol. 23, no. 8, pp. 1051-1061. https://doi.org/10.1038/ejhg.2014.239
Barthélémy F, Navarro C, Fayek R, Da Silva N, Roll P, Sigaudy S et al. Truncated prelamin A expression in HGPS-like patients: A transcriptional study. European Journal of Human Genetics. 2015 Jan 1;23(8):1051-1061. https://doi.org/10.1038/ejhg.2014.239
Barthélémy, Florian ; Navarro, Claire ; Fayek, Racha ; Da Silva, Nathalie ; Roll, Patrice ; Sigaudy, Sabine ; Oshima, Junko ; Bonne, Gisèle ; Papadopoulou-Legbelou, Kyriaki ; Evangeliou, Athanasios E. ; Spilioti, Martha ; Lemerrer, Martine ; Wevers, Ron A. ; Morava-Kozicz, Eva ; Robaglia-Schlupp, Andrée ; Lévy, Nicolas ; Bartoli, Marc ; De Sandre-Giovannoli, Annachiara. / Truncated prelamin A expression in HGPS-like patients : A transcriptional study. In: European Journal of Human Genetics. 2015 ; Vol. 23, No. 8. pp. 1051-1061.
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AU - Morava-Kozicz, Eva

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