| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Service de Dermatologie, Hôpital Avicenne (F.C., L.L.), 93000 Bobigny; Département de Biologie Cellulaire, Institut Jacques Monod, UMR 7592 (B.B., J.-C.C.), 75005 Paris; and UPRES EA-3408, Université Paris XIII (F.C., L.L.); INSERM, U-402, Faculté de Médecine Saint-Antoine (E.D., O.L., C.V.), Laboratoire de Biologie Moléculaire, Fédération de Biochimie (O.L.), Service d’Hépatologie (O.C.), Service de Cardiologie (A.C.), Service d’Endocrinologie, EA 1533 Génétique de la Reproduction Humaine (S.C.-M.), Hôpital Saint-Antoine, 75012 Paris, France
Address all correspondence and requests for reprints to: Dr. Sophie Christin-Maitre, Service d’Endocrinologie, Hôpital Saint-Antoine, 184 rue du Fbg Saint-Antoine, 75571 Paris Cedex 12, France. E-mail: sophie.christin-maitre{at}sat.ap-hop-paris.fr.
A-Type lamins, arising from the LMNA gene, are intermediate filaments proteins that belong to the lamina, a ubiquitous nuclear network. Naturally occurring mutations in these proteins have been shown to be responsible for several distinct diseases that display skeletal and/or cardiac muscle or peripheral nerve involvement. These include familial partial lipodystrophy of the Dunnigan type and the mandibuloacral dysplasia syndrome. The pathophysiology of this group of diseases, often referred to as laminopathies, remains elusive.
We report a new condition in a 30-yr-old man exhibiting a previously undescribed heterozygous R133L LMNA mutation. His phenotype associated generalized acquired lipoatrophy with insulin-resistant diabetes, hypertriglyceridemia, hepatic steatosis, hypertrophic cardiomyopathy with valvular involvement, and disseminated whitish papules. Immunofluorescence microscopic analysis of the patient’s cultured skin fibroblasts revealed nuclear disorganization and abnormal distribution of A-type lamins, similar to that observed in patients harboring other LMNA mutations.
This observation broadens the clinical spectrum of laminopathies, pointing out the clinical variability of lipodystrophy and the unreported possibility of hypertrophic cardiomyopathy and skin involvement. It emphasizes the fact that the diagnosis of genetic alterations in A-type lamins requires careful and complete clinical and morphological investigations in patients regardless of the presenting signs.
This work was supported by grants from INSERM, Centre National de la Recherche Scientifique, Direction de la Recherche Clinique Assistance Publique-Hôpitaux de Paris, and the Association pour la Recherche sur le Cancer.
Abbreviations: CMT2B1, Autosomal recessive Charcot-Marie-Tooth disease type 2; DAPI, 4',6-diamidine-2'-phenylindole-dihydrochloride; DCM-CD, dilated cardiomyopathy with conduction defects; EDMD, Emery-Dreifuss muscular dystrophy; FPLD, familial partial lipodystrophy of the Dunnigan type; LGMD1B, limb-girdle muscular dystrophy type 1B; LV, left ventricular; mab, monoclonal antibody; MAD, mandibuloacral dysplasia.
This article has been cited by other articles:
 |
|
 |
|
  C.-Y. Tsao and J. R. Mendell Partial Epilepsy in an Adolescent Male With Limb-Girdle Muscular Dystrophy 1B J Child Neurol, March 1, 2009; 24(3): 346 - 348. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Decaudain, M.-C. Vantyghem, B. Guerci, A.-C. Hecart, M. Auclair, Y. Reznik, H. Narbonne, P.-H. Ducluzeau, B. Donadille, C. Lebbe, et al. New Metabolic Phenotypes in Laminopathies: LMNA Mutations in Patients with Severe Metabolic Syndrome J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4835 - 4844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Benedetti, I. Menditto, M. Degano, C. Rodolico, L. Merlini, A. D'Amico, L. Palmucci, A. Berardinelli, E. Pegoraro, C. P. Trevisan, et al. Phenotypic clustering of lamin A/C mutations in neuromuscular patients Neurology, September 18, 2007; 69(12): 1285 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. van Tintelen, R. A. Tio, W. S. Kerstjens-Frederikse, J. H. van Berlo, L. G. Boven, A. J.H. Suurmeijer, S. J. White, J. T. den Dunnen, G. J. te Meerman, Y. J. Vos, et al. Severe Myocardial Fibrosis Caused by a Deletion of the 5' End of the Lamin A/C Gene J. Am. Coll. Cardiol., June 26, 2007; 49(25): 2430 - 2439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Yaou, A. Toutain, T. Arimura, L. Demay, C. Massart, C. Peccate, A. Muchir, S. Llense, N. Deburgrave, F. Leturcq, et al. Multitissular involvement in a family with LMNA and EMD mutations: Role of digenic mechanism? Neurology, May 29, 2007; 68(22): 1883 - 1894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Halaschek-Wiener and A. Brooks-Wilson Progeria of Stem Cells: Stem Cell Exhaustion in Hutchinson-Gilford Progeria Syndrome J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2007; 62(1): 3 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Wilkie and E. C. Schirmer Guilt by Association: The Nuclear Envelope Proteome and Disease Mol. Cell. Proteomics, October 1, 2006; 5(10): 1865 - 1875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L.R.M. Verstraeten, J. L.V. Broers, M. A.M. van Steensel, S. Zinn-Justin, F. C.S. Ramaekers, P. M. Steijlen, M. Kamps, H. J.H. Kuijpers, D. Merckx, H. J.M. Smeets, et al. Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation Hum. Mol. Genet., August 15, 2006; 15(16): 2509 - 2522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 F. Muntoni, G. Bonne, L. G. Goldfarb, E. Mercuri, R. J. Piercy, M. Burke, R. B. Yaou, P. Richard, D. Recan, A. Shatunov, et al. Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins Brain, May 1, 2006; 129(5): 1260 - 1268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J.H. Van Berlo, J.W. Voncken, N. Kubben, J.L.V. Broers, R. Duisters, R.E.W. van Leeuwen, H.J.G.M. Crijns, F.C.S. Ramaekers, C.J. Hutchison, and Y.M. Pinto A-type lamins are essential for TGF-{beta}1 induced PP2A to dephosphorylate transcription factors Hum. Mol. Genet., October 1, 2005; 14(19): 2839 - 2849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Z. Al-Shali and R. A. Hegele Laminopathies and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1591 - 1595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A B Csoka, H Cao, P J Sammak, D Constantinescu, G P Schatten, and R A Hegele Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes J. Med. Genet., April 1, 2004; 41(4): 304 - 308. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garg Acquired and Inherited Lipodystrophies N. Engl. J. Med., March 18, 2004; 350(12): 1220 - 1234. [Full Text] [PDF]
|
|
|
|
|
|
C Goizet, R Ben Yaou, L Demay, P Richard, S Bouillot, M Rouanet, E Hermosilla, G Le Masson, A Lagueny, G Bonne, et al. A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia J. Med. Genet., March 1, 2004; 41(3): e29 - 29. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
