Skip Navigation


Human Molecular Genetics Advance Access originally published online on April 20, 2005
Human Molecular Genetics 2005 14(11):1503-1513; doi:10.1093/hmg/ddi159
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
14/11/1503    most recent
ddi159v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (58)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Navarro, C. L.
Right arrow Articles by Lévy, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Navarro, C. L.
Right arrow Articles by Lévy, N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors

Claire L. Navarro1, Juan Cadiñanos2, Annachiara De Sandre-Giovannoli3, Rafaëlle Bernard3, Sébastien Courrier4, Irène Boccaccio1, Amandine Boyer3, Wim J. Kleijer5, Anja Wagner5, Fabienne Giuliano6, Frits A. Beemer7, Jose M. Freije2, Pierre Cau1, Raoul C.M. Hennekam8, Carlos López-Otín2, Catherine Badens3,4 and Nicolas Lévy1,3,4,*

1Inserm U491, Faculté de Médecine de Marseille, Marseille, France, 2Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain, 3Département de Génétique Médicale, Hôpital d'enfants de la Timone, Marseille, France, 4Centre d'Enseignement et de Recherche en Génétique Médicale, Faculté de médecine, Marseille, France, 5Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands, 6Service de Génétique Médicale, CHU Nice, Hôpital de l'Archet, Nice, France, 7Clinical Genetics Center, University Medical Center, Utrecht, The Netherlands and 8Department of Pediatrics and Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands

* To whom correspondence should be addressed at: Inserm U491: ‘Génétique Médicale et Développement’, Faculté de Médecine de Marseille, 13385 Marseille Cedex 05, France. Tel: +33 491786894; Fax: +33 491804319; Email: nicolas.levy{at}medecine.univ-mrs.fr

Received February 26, 2005; Accepted April 11, 2005

Restrictive dermopathy (RD) is characterized by intrauterine growth retardation, tight and rigid skin with prominent superficial vessels, bone mineralization defects, dysplastic clavicles, arthrogryposis and early neonatal death. In two patients affected with RD, we recently reported two different heterozygous splicing mutations in the LMNA gene, leading to the production and accumulation of truncated Prelamin A. In other patients, a single nucleotide insertion was identified in ZMPSTE24. This variation is located in a homopolymeric repeat of thymines and introduces a premature termination codon. ZMPSTE24 encodes an endoprotease essential for the post-translational cleavage of the Lamin A precursor and the production of mature Lamin A. However, the autosomal recessive inheritance of RD suggested that a further molecular defect was present either in the second ZMPSTE24 allele or in another gene involved in Lamin A processing. Here, we report new findings in RD linked to ZMPSTE24 mutations. Ten RD patients were analyzed including seven from a previous series and three novel patients. All were found to be either homozygous or compound heterozygous for ZMPSTE24 mutations. We report three novel ‘null’ mutations as well as the recurrent thymine insertion. In all cases, we find a complete absence of both ZMPSTE24 and mature Lamin A associated with Prelamin A accumulation. Thus, RD is either a primary or a secondary laminopathy, caused by dominant de novo LMNA mutations or, more frequently, recessive null ZMPSTE24 mutations, most of which lie in a mutation hotspot within exon 9. The accumulation of truncated or normal length Prelamin A is, therefore, a shared pathophysiological feature in recessive and dominant RD. These findings have an important impact on our knowledge of the pathophysiology in Progeria and related disorders and will help direct the development of therapeutic approaches.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
C. Coffinier, S. E. Hudon, R. Lee, E. A. Farber, C. Nobumori, J. H. Miner, D. A. Andres, H. P. Spielmann, C. A. Hrycyna, L. G. Fong, et al.
A Potent HIV Protease Inhibitor, Darunavir, Does Not Inhibit ZMPSTE24 or Lead to an Accumulation of Farnesyl-prelamin A in Cells
J. Biol. Chem., April 11, 2008; 283(15): 9797 - 9804.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
Y. Liu, Y. Wang, A. E. Rusinol, M. S. Sinensky, J. Liu, S. M. Shell, and Y. Zou
Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A
FASEB J, February 1, 2008; 22(2): 603 - 611.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Coffinier, S. E. Hudon, E. A. Farber, S. Y. Chang, C. A. Hrycyna, S. G. Young, and L. G. Fong
From the Cover: HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells
PNAS, August 14, 2007; 104(33): 13432 - 13437.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
B. C. Capell, F. S. Collins, and E. G. Nabel
Mechanisms of Cardiovascular Disease in Accelerated Aging Syndromes
Circ. Res., July 6, 2007; 101(1): 13 - 26.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. L. Moulson, M.-H. Lin, J. M. White, E. P. Newberry, N. O. Davidson, and J. H. Miner
Keratinocyte-specific Expression of Fatty Acid Transport Protein 4 Rescues the Wrinkle-free Phenotype in Slc27a4/Fatp4 Mutant Mice
J. Biol. Chem., May 25, 2007; 282(21): 15912 - 15920.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. G. Young, M. Meta, S. H. Yang, and L. G. Fong
Prelamin A Farnesylation and Progeroid Syndromes
J. Biol. Chem., December 29, 2006; 281(52): 39741 - 39745.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
Y. Liu, A. Rusinol, M. Sinensky, Y. Wang, and Y. Zou
DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A
J. Cell Sci., November 15, 2006; 119(22): 4644 - 4649.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. L. Navarro, P. Cau, and N. Levy
Molecular bases of progeroid syndromes
Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R151 - R161.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
A. E. Rusinol and M. S. Sinensky
Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors.
J. Cell Sci., August 15, 2006; 119(Pt 16): 3265 - 3272.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. T. Nitta, S. A. Jameson, B. A. Kudlow, L. A. Conlan, and B. K. Kennedy
Stabilization of the Retinoblastoma Protein by A-Type Nuclear Lamins Is Required for INK4A-Mediated Cell Cycle Arrest.
Mol. Cell. Biol., July 1, 2006; 26(14): 5360 - 5372.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. L. V. Broers, F. C. S. Ramaekers, G. Bonne, R. B. Yaou, and C. J. Hutchison
Nuclear lamins: laminopathies and their role in premature ageing.
Physiol Rev, July 1, 2006; 86(3): 967 - 1008.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. F. Morel, M. A. Thomas, H. Cao, C. H. O'Neil, J. G. Pickering, W. D. Foulkes, and R. A. Hegele
A LMNA Splicing Mutation in Two Sisters with Severe Dunnigan-Type Familial Partial Lipodystrophy Type 2
J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2689 - 2695.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
L. G. Fong, D. Frost, M. Meta, X. Qiao, S. H. Yang, C. Coffinier, and S. G. Young
A Protein Farnesyltransferase Inhibitor Ameliorates Disease in a Mouse Model of Progeria
Science, March 17, 2006; 311(5767): 1621 - 1623.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
A. D. Basso, P. Kirschmeier, and W. R. Bishop
Thematic review series: Lipid Posttranslational Modifications. Farnesyl transferase inhibitors
J. Lipid Res., January 1, 2006; 47(1): 15 - 31.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. G. Young, L. G. Fong, and S. Michaelis
Thematic Review Series: Lipid Posttranslational Modifications. Prelamin A, Zmpste24, misshapen cell nuclei, and progeria--new evidence suggesting that protein farnesylation could be important for disease pathogenesis
J. Lipid Res., December 1, 2005; 46(12): 2531 - 2558.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. N. Jacob, F. Baptista, H. G. dos Santos, J. Oshima, A. K. Agarwal, and A. Garg
Phenotypic Heterogeneity in Body Fat Distribution in Patients with Atypical Werner's Syndrome Due to Heterozygous Arg133Leu Lamin A/C Mutation
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6699 - 6706.
[Abstract] [Full Text] [PDF]

Home page
 Arch DermatolHome page
S. Armbrust, R. Hoffmann, F. Jochum, L. M. Neumann, and C. Fusch
Defective Prelamin A Processing Resulting From LMNA or ZMPSTE24 Mutations as the Cause of Restrictive Dermopathy--Reply
Arch Dermatol, November 1, 2005; 141(11): 1474 - 1474.
[Full Text] [PDF]

Home page
 Arch DermatolHome page
N. Levy, C. Lopez-Otin, and R. C. M. Hennekam
Defective Prelamin A Processing Resulting From LMNA or ZMPSTE24 Mutations as the Cause of Restrictive Dermopathy
Arch Dermatol, November 1, 2005; 141(11): 1473 - 1474.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. P. Mallampalli, G. Huyer, P. Bendale, M. H. Gelb, and S. Michaelis
Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome
PNAS, October 4, 2005; 102(40): 14416 - 14421.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. I. Toth, S. H. Yang, X. Qiao, A. P. Beigneux, M. H. Gelb, C. L. Moulson, J. H. Miner, S. G. Young, and L. G. Fong
Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes
PNAS, September 6, 2005; 102(36): 12873 - 12878.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.