| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Departments of Neurology (Dr. Felice) and Pathology (Dr. Grunnet) and the Division of Human Genetics (R.C. Schwartz), University of Connecticut School of Medicine, Farmington; the DNA Diagnostic Laboratory, Department of Pediatrics (Dr. Brown), Carolinas Medical Center, Charlotte, NC; and the Division of Pediatric Neurology (Dr. Leicher), Connecticut Children’s Medical Center, Hartford.
Address correspondence and reprint requests to Dr. Kevin J. Felice, Department of Neurology, University of Connecticut School of Medicine, Farmington, CT 06035-1840; e-mail: felice{at}nso.uchc.edu
BACKGROUND: Autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD-AD) is a disorder characterized clinically by humeropelvic weakness, contractures, and cardiomyopathy, and genetically by mutations in the lamin A/C gene on 1q21.2-q21.3. Of the 14 lamin A/C gene mutations reported thus far, the four involving the rod domain have been associated with isolated cardiomyopathy and conduction-system disease. This is the first report of rod domain mutations in patients with the full EDMD-AD phenotype.
METHODS: Clinical, pathologic, and genetic data are provided on two families with EDMD-AD.
RESULTS: In both families, the full clinical spectrum of EDMD-AD was demonstrated. For the proband in family 1, sequence analysis detected a mutation within exon 2 of the lamin A/C gene. The missense mutation was due to a A448C base substitution causing a Thr150Pro amino acid change. For the proband of family 2, sequence analysis detected an in-frame 3-bp deletion (AAG 778-780 or 781-783) removing one of two adjacent lysine residues (K 260 or 261) of exon 4. Both mutations were in the central rod domain of the lamin A/C gene.
CONCLUSIONS: Mutations in the rod domain of the lamin A/C gene may cause the full clinical spectrum of EDMD-AD.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 M. Krasnianski, U. Ehrt, S. Neudecker, and S. Zierz Alfred Hauptmann, Siegfried Thannhauser, and an Endangered Muscular Disorder Arch Neurol, July 1, 2004; 61(7): 1139 - 1141. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Arbustini, A. Pilotto, A. Repetto, M. Grasso, A. Negri, M. Diegoli, C. Campana, L. Scelsi, E. Baldini, A. Gavazzi, et al. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease J. Am. Coll. Cardiol., March 20, 2002; 39(6): 981 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Goldman, Y. Gruenbaum, R. D. Moir, D. K. Shumaker, and T. P. Spann Nuclear lamins: building blocks of nuclear architecture Genes & Dev., March 1, 2002; 16(5): 533 - 547. [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Lelliott, L. Logie, C. P. Sewter, D. Berger, P. Jani, F. Blows, S. O'Rahilly, and A. Vidal-Puig Lamin Expression in Human Adipose Cells in Relation to Anatomical Site and Differentiation State J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 728 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gamez, C. Navarro, A.L. Andreu, J.M. Fernandez, L. Palenzuela, S. Tejeira, R. Fernandez-Hojas, S. Schwartz, C. Karadimas, S. DiMauro, et al. Autosomal dominant limb-girdle muscular dystrophy: A large kindred with evidence for anticipation Neurology, February 27, 2001; 56(4): 450 - 454. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
