This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schönberger, J. Articles by Seidman, C. E. Search for Related Content PubMed PubMed Citation Articles by Schönberger, J. Articles by Seidman, C. E. Related Collections Congestive Myocardial cardiomyopathy disease Genetics of cardiovascular disease Heart failure - basic studies

(Circulation. 2000;101:1812.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Dilated Cardiomyopathy and Sensorineural Hearing Loss

A Heritable Syndrome That Maps to 6q23–24

Jost Schönberger, MD; Hara Levy, MD; Ekkehard Grünig, MD; Somkiat Sangwatanaroj, MD; Diane Fatkin, MD; Calum MacRae, MBChB; Hinrich Stäcker, MD, PhD; Christopher Halpin, PhD; Roland Eavey, MD; Edward F. Philbin, MD; Hugo Katus, MD; J. G. Seidman, PhD; Christine E. Seidman, MD

From the Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School (J.S., H.L., S.S., D.F., C.M., J.G.S., C.E.S.), the Department of Pulmonary Medicine, Children’s Hospital (H.L.), the Massachusetts Eye and Ear Infirmary (H.S., C.H., R.E.), and the Cardiovascular Division and Howard Hughes Medical Institute, Brigham and Women’s Hospital, (C.E.S.), Boston, Mass; the University of Heidelberg, Department of Medicine III, Heidelberg, Germany (E.G.); the Section of Heart Failure and Cardiac Transplantation, Henry Ford Hospital, Detroit, Mich (E.F.P.); and the University of Lübeck, Department of Medicine II, Lübeck, Germany (H.K.).

Correspondence to Christine E. Seidman, MD, Dept of Genetics/Alpert Room 533, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115. E-mail cseidman{at}rascal.med.harvard.edu

Background—Dilated cardiomyopathy (DCM) and sensorineural hearing loss (SNHL) are prevalent disorders that occur alone or as components of complex multisystem syndromes. Multiple genetic loci have been identified that, when mutated, cause DCM or SNHL. However, the isolated coinheritance of these phenotypes has not been previously recognized.

Methods and Results—Clinical evaluations of 2 kindreds demonstrated autosomal-dominant transmission and age-related penetrance of both SNHL and DCM in the absence of other disorders. Moderate-to-severe hearing loss was evident by late adolescence, whereas ventricular dysfunction produced progressive congestive heart failure after the fourth decade. DNA samples from the larger kindred (29 individuals) were used to perform a genome-wide linkage study. Polymorphic loci on chromosome 6q23 to 24 were coinherited with the disease (maximum logarithm of odds score, 4.88 at locus D6S2411). The disease locus must lie within a 2.8 cM interval between loci D6S975 and D6S292, a location that overlaps an SNHL disease locus (DFNA10). However, DFNA10 does not cause cardiomyopathy. The epicardin gene, which encodes a transcription factor expressed in the myocardium and cochlea, was assessed as a candidate gene by nucleotide sequence analysis; no mutations were identified.

Conclusions—A syndrome of juvenile-onset SNHL and adult-onset DCM is caused by a mutation at 6q23 to 24 (locus designated CMD1J). Recognition of this cardioauditory disorder allows for the identification of young adults at risk for serious heart disease, thereby enabling early intervention. Definition of the molecular cause of this syndrome may provide new information about important cell physiology common to both the ear and heart.

Key Words: cardiomyopathy • hearing loss, sensorineural • genetics

This article has been cited by other articles:

				L. Zhang, A. Hu, H. Yuan, L. Cui, G. Miao, X. Yang, L. Wang, J. Liu, X. Liu, S. Wang, et al. A Missense Mutation in the CHRM2 Gene Is Associated With Familial Dilated Cardiomyopathy Circ. Res., June 6, 2008; 102(11): 1426 - 1432. [Abstract] [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]

				S A Mohiddin, Z M Ahmed, A J Griffith, D Tripodi, T B Friedman, L Fananapazir, and R J Morell Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6) J. Med. Genet., April 1, 2004; 41(4): 309 - 314. [Full Text] [PDF]

				P. A. Doevendans Genetic Polymorphisms and Cardiac Failure Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2003; 7(1): 23 - 29. [PDF]

				D. Fatkin and R. M. Graham Molecular Mechanisms of Inherited Cardiomyopathies Physiol Rev, October 1, 2002; 82(4): 945 - 980. [Abstract] [Full Text] [PDF]

				K. A. Crispell, E. L. Hanson, K. Coates, W. Toy, and R. E. Hershberger Periodic rescreening is indicated for family members at risk of developing familial dilated cardiomyopathy J. Am. Coll. Cardiol., May 1, 2002; 39(9): 1503 - 1507. [Abstract] [Full Text] [PDF]

				K. F. Benson and K. Chada Molecular Characterization of the Mouse In(10)17Rk Inversion and Identification of a Novel Muscle-Specific Gene at the Proximal Breakpoint Genetics, January 1, 2002; 160(1): 279 - 287. [Abstract] [Full Text] [PDF]

				S. Wayne, N. G. Robertson, F. DeClau, N. Chen, K. Verhoeven, S. Prasad, L. Tranebjarg, C. C. Morton, A. F. Ryan, G. Van Camp, et al. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus Hum. Mol. Genet., February 1, 2001; 10(3): 195 - 200. [Abstract] [Full Text] [PDF]

				M KOMAJDA Genetics of dilated cardiomyopathy: a molecular maze? Heart, November 1, 2000; 84(5): 463 - 464. [Full Text]