EXPEDITED REVIEW
Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction
Matteo Vatta, PhD*,
Bhagyalaxmi Mohapatra, PhD*,
Shinawe Jimenez, MD*,
Ximena Sanchez, PhD*,
Georgine Faulkner, PhD ,
Zeev Perles, MD*,
Gianfranco Sinagra, MD ,
Jiuann-Huey Lin, MD*,
Thuy M. Vu, BS*,
Qiang Zhou, PhD||,
Karla R. Bowles, PhD*,
Andrea Di Lenarda, MD,
Lisa Schimmenti, MD¶,
Michelle Fox, MS||,
Michelle A. Chrisco, BS*,
Ross T. Murphy, MD#,
William McKenna, MD#,
Perry Elliott, MD#,
Neil E. Bowles, PhD*,
Ju Chen, PhD||,
Giorgio Valle, PhD** and
Jeffrey A. Towbin, MD, FACC* ,*
* Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, Texas, USA;
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
Department of Cardiology, Ospedale Maggiore, Trieste, Italy
|| Institute of Molecular Medicine and Department of Medicine, University of California at San Diego, School of Medicine, La Jolla, California, USA
¶ Department of Pediatrics (Genetics), University of California at Los Angeles, Los Angeles, California, USA
# Department of Cardiological Sciences, St. George's Hospital Medical School, London, United Kingdom
** CRIBI Biotechnology Centre, Universita degli Studi di Padova, Padova, Italy
Manuscript received July 15, 2003;
revised manuscript received October 6, 2003,
accepted October 9, 2003.
* Reprint requests and correspondence: Dr. Jeffrey A. Towbin, Pediatric Cardiology, Texas Children's Hospital, 6621 Fannin Street, F.C. 430.09, Houston, Texas 77030, USA.
jtowbin{at}bcm.tmc.edu
OBJECTIVES: We evaluated the role of Cypher/ZASP in the pathogenesis of dilated cardiomyopathy (DCM) with or without isolated non-compaction of the left ventricular myocardium (INLVM).
BACKGROUND: Dilated cardiomyopathy, characterized by left ventricular dilation and systolic dysfunction with signs of heart failure, is genetically transmitted in 30% to 40% of cases. Genetic heterogeneity has been identified with mutations in multiple cytoskeletal and sarcomeric genes causing the phenotype. In addition, INLVM with a hypertrophic dilated left ventricle, ventricular dysfunction, and deep trabeculations, is also inherited, and the genes identified to date differ from those causing DCM. Cypher/ZASP is a newly identified gene encoding a protein that is a component of the Z-line in both skeletal and cardiac muscle.
METHODS: Diagnosis of DCM was performed by echocardiogram, electrocardiogram, and physical examination. In addition, levels of the muscular isoform of creatine kinase were measured to evaluate for skeletal muscle involvement. Cypher/ZASP was screened by denaturing high performance liquid chromatography (DHPLC) and direct deoxyribonucleic acid sequencing.
RESULTS: We identified and screened 100 probands with left ventricular dysfunction. Five mutations in six probands (6% of cases) were identified in patients with familial or sporadic DCM or INLVM. In vitro studies showed cytoskeleton disarray in cells transfected with mutated Cypher/ZASP.
CONCLUSIONS: These data suggest that mutated Cypher/ZASP can cause DCM and INLVM and identify a mechanistic basis.
|
Abbreviations and Acronyms
| | BAC | = bacterial artificial chromosome | | DCM | = dilated cardiomyopathy | | DNA | = deoxyribonucleic acid | | DHPLC | = denaturing high performance liquid chromatography | | GFP | = green fluorescence protein | | INLVM | = isolated non-compaction of the left ventricular myocardium | | LVNC | = left ventricular non-compaction | | MRI | = magnetic resonance imaging | | mRNA | = messenger ribonucleic acid | | NYHA | = New York Heart Association | | PCR | = polymerase chain reaction | | RNA | = ribonucleic acid | | RT | = reverse transcription | | SDS | = sodium dodecylsulfate |
|
This article has been cited by other articles:
|
|
|
|
 
L. M. Dellefave, P. Pytel, S. Mewborn, B. Mora, D. L. Guris, S. Fedson, D. Waggoner, I. Moskowitz, and E. M. McNally
Sarcomere Mutations in Cardiomyopathy With Left Ventricular Hypertrabeculation
Circ Cardiovasc Genet,
October 1, 2009;
2(5):
442 - 449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Moulik, M. Vatta, S. H. Witt, A. M. Arola, R. T. Murphy, W. J. McKenna, A. M. Boriek, K. Oka, S. Labeit, N. E. Bowles, et al.
ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene.
J. Am. Coll. Cardiol.,
July 21, 2009;
54(4):
325 - 333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Bos, J. A. Towbin, and M. J. Ackerman
Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy.
J. Am. Coll. Cardiol.,
July 14, 2009;
54(3):
201 - 211.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Arimura, N. Inagaki, T. Hayashi, D. Shichi, A. Sato, K. Hinohara, M. Vatta, J. A. Towbin, T. Chikamori, A. Yamashina, et al.
Impaired binding of ZASP/Cypher with phosphoglucomutase 1 is associated with dilated cardiomyopathy
Cardiovasc Res,
July 1, 2009;
83(1):
80 - 88.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-F. Han and M. C. Beckerle
The ALP-Enigma Protein ALP-1 Functions in Actin Filament Organization to Promote Muscle Structural Integrity in Caenorhabditis elegans
Mol. Biol. Cell,
May 1, 2009;
20(9):
2361 - 2370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zheng, H. Cheng, X. Li, J. Zhang, L. Cui, K. Ouyang, L. Han, T. Zhao, Y. Gu, N. D. Dalton, et al.
Cardiac-specific ablation of Cypher leads to a severe form of dilated cardiomyopathy with premature death
Hum. Mol. Genet.,
February 15, 2009;
18(4):
701 - 713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. von Nandelstadh, M. Ismail, C. Gardin, H. Suila, I. Zara, A. Belgrano, G. Valle, O. Carpen, and G. Faulkner
A Class III PDZ Binding Motif in the Myotilin and FATZ Families Binds Enigma Family Proteins: a Common Link for Z-Disc Myopathies
Mol. Cell. Biol.,
February 1, 2009;
29(3):
822 - 834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Priori, C. Napolitano, S. E. Humphries, and J. Skipworth
CHAPTER 9 Genetics of Cardiovascular Diseases
ESC Textbook of Cardiovascular Medicine,
January 1, 2009;
2(1):
med-9780199566990-chapter - med-9780199566990-chapter.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. M. Hess, W. McKenna, and H.-P. Schultheiss
CHAPTER 18 Myocardial Disease
ESC Textbook of Cardiovascular Medicine,
January 1, 2009;
2(1):
med-9780199566990-chapter - med-9780199566990-chapter.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. M. Boe, L. Rhee-Morris, D. Towner, and A. J. Moon-Grady
Prenatal Diagnosis of Omphalocele and Left Atrial Isomerism (Polysplenia) Including Complex Congenital Heart Disease With Ventricular Noncompaction Cardiomyopathy
J. Ultrasound Med.,
July 1, 2008;
27(7):
1117 - 1121.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Klaassen, S. Probst, E. Oechslin, B. Gerull, G. Krings, P. Schuler, M. Greutmann, D. Hurlimann, M. Yegitbasi, L. Pons, et al.
Mutations in Sarcomere Protein Genes in Left Ventricular Noncompaction
Circulation,
June 3, 2008;
117(22):
2893 - 2901.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Morimoto
Sarcomeric proteins and inherited cardiomyopathies
Cardiovasc Res,
March 1, 2008;
77(4):
659 - 666.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. K. Kohli, A. A. Pantazis, J. S. Shah, B. Adeyemi, G. Jackson, W. J. McKenna, S. Sharma, and P. M. Elliott
Diagnosis of left-ventricular non-compaction in patients with left-ventricular systolic dysfunction: time for a reappraisal of diagnostic criteria?
Eur. Heart J.,
January 1, 2008;
29(1):
89 - 95.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mery, O. Taghli-Lamallem, K. A. Clark, M. C. Beckerle, X. Wu, K. Ocorr, and R. Bodmer
The Drosophila muscle LIM protein, Mlp84B, is essential for cardiac function
J. Exp. Biol.,
January 1, 2008;
211(1):
15 - 23.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Jani and F. Schock
Zasp is required for the assembly of functional integrin adhesion sites
J. Cell Biol.,
December 31, 2007;
179(7):
1583 - 1597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Kley, Y. Hellenbroich, P. F. M. van der Ven, D. O. Furst, A. Huebner, V. Bruchertseifer, S. A. Peters, C. M. Heyer, J. Kirschner, R. Schroder, et al.
Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients
Brain,
December 1, 2007;
130(12):
3250 - 3264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. M. Hoedemaekers, K. Caliskan, D. Majoor-Krakauer, I. van de Laar, M. Michels, M. Witsenburg, F. J. ten Cate, M. L. Simoons, and D. Dooijes
Cardiac {beta}-myosin heavy chain defects in two families with non-compaction cardiomyopathy: linking non-compaction to hypertrophic, restrictive, and dilated cardiomyopathies
Eur. Heart J.,
November 2, 2007;
28(22):
2732 - 2737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. H. Robin, P. B. Tabereaux, R. Benza, and B. R. Korf
Genetic Testing in Cardiovascular Disease
J. Am. Coll. Cardiol.,
August 21, 2007;
50(8):
727 - 737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Monserrat, M. Hermida-Prieto, X. Fernandez, I. Rodriguez, C. Dumont, L. Cazon, M. G. Cuesta, C. Gonzalez-Juanatey, J. Peteiro, N. Alvarez, et al.
Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects
Eur. Heart J.,
August 2, 2007;
28(16):
1953 - 1961.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Griggs, A. Vihola, P. Hackman, K. Talvinen, H. Haravuori, G. Faulkner, B. Eymard, I. Richard, D. Selcen, A. Engel, et al.
Zaspopathy in a large classic late-onset distal myopathy family
Brain,
June 1, 2007;
130(6):
1477 - 1484.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Y. Boateng, R. J. Belin, D. L. Geenen, K. B. Margulies, J. L. Martin, M. Hoshijima, P. P. de Tombe, and B. Russell
Cardiac dysfunction and heart failure are associated with abnormalities in the subcellular distribution and amounts of oligomeric muscle LIM protein
Am J Physiol Heart Circ Physiol,
January 1, 2007;
292(1):
H259 - H269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Lorsheyd, M.-J. M. Cramer, B. K. Velthuis, E.-J. P. Vonken, J. van der Smagt, P. van Tintelen, and R. N.W. Hauer
Familial occurrence of isolated non-compaction cardiomyopathy
Eur J Heart Fail,
December 1, 2006;
8(8):
826 - 831.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Towbin, A. M. Lowe, S. D. Colan, L. A. Sleeper, E. J. Orav, S. Clunie, J. Messere, G. F. Cox, P. R. Lurie, D. Hsu, et al.
Incidence, causes, and outcomes of dilated cardiomyopathy in children.
JAMA,
October 18, 2006;
296(15):
1867 - 1876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Donahue, D. A. Marchuk, and H. A. Rockman
Redefining Heart Failure: The Utility of Genomics
J. Am. Coll. Cardiol.,
October 3, 2006;
48(7):
1289 - 1298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lilje, V. Razek, J. J. Joyce, T. Rau, B. F. Finckh, F. Weiss, C. R. Habermann, J. C. Rice, and J. Weil
Complications of non-compaction of the left ventricular myocardium in a paediatric population: a prospective study
Eur. Heart J.,
August 1, 2006;
27(15):
1855 - 1860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. T. Ellinor, S. Sasse-Klaassen, S. Probst, B. Gerull, J. T. Shin, A. Toeppel, A. Heuser, B. Michely, D. M. Yoerger, B.-S. Song, et al.
A Novel Locus for Dilated Cardiomyopathy, Diffuse Myocardial Fibrosis, and Sudden Death on Chromosome 10q25-26
J. Am. Coll. Cardiol.,
July 4, 2006;
48(1):
106 - 111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hoshijima
Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures
Am J Physiol Heart Circ Physiol,
April 1, 2006;
290(4):
H1313 - H1325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Priori and C. Napolitano
Role of Genetic Analyses in Cardiology: Part I: Mendelian Diseases: Cardiac Channelopathies
Circulation,
February 28, 2006;
113(8):
1130 - 1135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Finsterer and C. Stollberger
Unsolved issues of left ventricular hypertrabeculation/noncompaction
Eur J Echocardiogr,
January 1, 2006;
7(1):
5 - 6.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Torsoni, T. M. Marin, L. A. Velloso, and K. G. Franchini
RhoA/ROCK signaling is critical to FAK activation by cyclic stretch in cardiac myocytes
Am J Physiol Heart Circ Physiol,
October 1, 2005;
289(4):
H1488 - H1496.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Ward, R. Murphy, D. Pellerin, and P. Elliott
Evident, but poorly defined: left ventricular hypertrabeculation/noncompaction and its diagnostic criteria: reply
Eur. Heart J.,
June 1, 2005;
26(11):
1144 - 1145.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. L. Burkett and R. E. Hershberger
Clinical and genetic issues in familial dilated cardiomyopathy
J. Am. Coll. Cardiol.,
April 5, 2005;
45(7):
969 - 981.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Fonseca, R. Y. Inoue, C. B. Kobarg, D. P. Crosara-Alberto, J. Kobarg, and K. G. Franchini
Targeting to C-Terminal Myosin Heavy Chain May Explain Mechanotransduction Involving Focal Adhesion Kinase in Cardiac Myocytes
Circ. Res.,
January 7, 2005;
96(1):
73 - 81.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Murphy, R. Thaman, J. G. Blanes, D. Ward, E. Sevdalis, E. Papra, A. Kiotsekolglou, M. T. Tome, D. Pellerin, W. J. McKenna, et al.
Natural history and familial characteristics of isolated left ventricular non-compaction
Eur. Heart J.,
January 2, 2005;
26(2):
187 - 192.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hayashi, T. Arimura, M. Itoh-Satoh, K. Ueda, S. Hohda, N. Inagaki, M. Takahashi, H. Hori, M. Yasunami, H. Nishi, et al.
Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy
J. Am. Coll. Cardiol.,
December 7, 2004;
44(11):
2192 - 2201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Finsterer and C. Stollberger
Do cypher gene mutations cause left ventricular noncompaction with subclinical myopathy?
J. Am. Coll. Cardiol.,
September 1, 2004;
44(5):
1139 - 1139.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Vatta, B. Mohapatra, S. Jimenez, X. Sanchez, N. Bowles, K. R. Bowles, and J. A. Towbin
Reply
J. Am. Coll. Cardiol.,
September 1, 2004;
44(5):
1139 - 1140.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Klaavuniemi, A. Kelloniemi, and J. Ylanne
The ZASP-like Motif in Actinin-associated LIM Protein Is Required for Interaction with the {alpha}-Actinin Rod and for Targeting to the Muscle Z-line
J. Biol. Chem.,
June 18, 2004;
279(25):
26402 - 26410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sasse-Klaassen, S. Probst, B. Gerull, E. Oechslin, P. Nurnberg, A. Heuser, R. Jenni, H. C. Hennies, and L. Thierfelder
Novel Gene Locus for Autosomal Dominant Left Ventricular Noncompaction Maps to Chromosome 11p15
Circulation,
June 8, 2004;
109(22):
2720 - 2723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Finsterer, C. Stollberger, G. Blazek, R. Pignatelli, C. J. McMahon, W. J. Dreyer, S. W. Denfield, J. Wu, J. Price, H. El Said, et al.
Left Ventricular Noncompaction Suggests Myopathy * Response
Circulation,
April 27, 2004;
109(16):
e201 - e202.
[Full Text]
[PDF]
|
|
|
|
