| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
sarcoglycan mutations
a Department of
Neuromuscular Diseases, Istituto Nazionale Neurologico "C Besta",
Via Celoria 11, 20133 Milano, Italy, b Department of Rehabilitative Cardiology,
Ospedale Generale "Moriggia-Pelascini", Gravedona, Como, Italy, c Istituto Scientifico "Eugenio
Medea", Bosisio Parini, Lecco, Italy
Correspondence to: Dr Mora
Revised version received 4 August 1999;
Accepted for publication 27 August 1999
Two young males with limb-girdle muscular dystrophy (LGMD)
resulting from sarcoglycan deficiency died at 27 (patient 1) and 18 years (patient 2) of severe cardiomyopathy. Genetic analysis showed
that they were compound heterozygotes for mutations in the 
sarcoglycan gene. One of these mutations, an 8 bp duplication in exon
3, was common to both patients. The second mutation in patient 2 was a
4 bp deletion at the splice donor site of intron 2, not reported
previously. Patient 2 had more severe heart and skeletal muscle defects
with faster deterioration; no sarcoglycans were detected in his
skeletal muscle. The second mutation in patient 1, inferred because the
unaffected father carries the 8 bp duplication, was not found. In
patient 1, both heart and skeletal muscle were analysed and showed
reduction of all sarcoglycans in both tissues and incorrect
localisation of 
and 
sarcoglycans in heart. Therefore mutations
in one sarcoglycan gene can disrupt the entire sarcoglycan complex in
both skeletal and cardiac muscle. Differing expression patterns of
sarcoglycan components in heart and skeletal muscle could be the result
of alternatively spliced transcripts in these tissues. By sequencing an
alternative transcript, highly expressed in the heart and skeletal
muscle of patient 1, we found an 87 bp cryptic exon not previously
reported. Although cardiomyopathy can result from mutations in and
sarcoglycans, we show for the first time that the condition can
also be caused by mutations in the sarcoglycan gene. This report
therefore expands the phenotype of sarcoglycanopathies and suggests
that cardiac function in LGMD patients with defective sarcoglycan
expression should be monitored.
This article has been cited by other articles:
|
|
 |
|
  J. Davis, M. V. Westfall, D. Townsend, M. Blankinship, T. J. Herron, G. Guerrero-Serna, W. Wang, E. Devaney, and J. M. Metzger Designing Heart Performance by Gene Transfer Physiol Rev, October 1, 2008; 88(4): 1567 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Lapidos, R. Kakkar, and E. M. McNally The Dystrophin Glycoprotein Complex: Signaling Strength and Integrity for the Sarcolemma Circ. Res., April 30, 2004; 94(8): 1023 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Vatta, B. Mohapatra, S. Jimenez, X. Sanchez, G. Faulkner, Z. Perles, G. Sinagra, J.-H. Lin, T. M. Vu, Q. Zhou, et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction J. Am. Coll. Cardiol., December 3, 2003; 42(11): 2014 - 2027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Boito, M Fanin, G Siciliano, C Angelini, and E Pegoraro Novel sarcoglycan gene mutations in a large cohort of Italian patients J. Med. Genet., May 1, 2003; 40(5): e67 - 67. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Muntoni Cardiac Complications of Childhood Myopathies J Child Neurol, March 1, 2003; 18(3): 191 - 202. [Abstract] [PDF]
|
|
|
|
 |
|
 N.E. Bowles The molecular biology of dilated cardiomyopathy Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I2 - I7. [Abstract] [PDF]
|
|
|
|
 |
|
 E. P. Moiseeva Adhesion receptors of vascular smooth muscle cells and their functions Cardiovasc Res, December 1, 2001; 52(3): 372 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Allamand and K. P. Campbell Animal models for muscular dystrophy: valuable tools for the development of therapies Hum. Mol. Genet., October 1, 2000; 9(16): 2459 - 2467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-H. Lee, C. Badorff, and K. U. Knowlton Dissociation of Sarcoglycans and the Dystrophin Carboxyl Terminus From the Sarcolemma in Enteroviral Cardiomyopathy Circ. Res., September 15, 2000; 87(6): 489 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Barresi, S. A. Moore, C. A. Stolle, J. R. Mendell, and K. P. Campbell Expression of gamma -Sarcoglycan in Smooth Muscle and Its Interaction with the Smooth Muscle Sarcoglycan-Sarcospan Complex J. Biol. Chem., December 1, 2000; 275(49): 38554 - 38560. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
