BACKGROUND: Dilated cardiomyopathy, characterized by ventricular dilatation and decreased systolic contraction, is twofold to threefold more common as a cause of heart failure than hypertrophic cardiomyopathy and costs several billion dollars annually. The idiopathic form occurring early in life, with a 75% mortality in 5 years, is a common reason for transplantation. It is estimated that at least 20% of cases are familial. METHODS AND RESULTS: A family of 46 members spanning four generations underwent history and physical examinations, echocardiographic analysis, and blood sampling for genotyping. Diagnostic criteria, detected by echocardiography, consisted of ventricular dimension of > or = 2.7 cm/m2 with an ejection fraction < or = 50% in the absence of other potential causes. DNA from all members was analyzed by polymerase chain reaction for amplification of short tandem-repeat polymorphic markers located every 10 cM throughout the human genome. Assuming a penetrance of 90%, linkage analysis was performed to map the responsible chromosomal locus. Linkage analysis, after 412 markers were analyzed, indicated the locus to be on chromosome 1q32, with a peak multipoint logarithm of the odds score at D1S414 of 6.37. CONCLUSIONS: The locus identified in this study for familial dilated cardiomyopathy, 1q32, is rich in candidate genes, such as MEF-2, renin, and helix loop helix DNA binding protein MYF-4. Identification of the genetic defect could provide insight into the molecular basis for the cardiac dilatory response in both familial and acquired disorders.
BACKGROUND:Dilated cardiomyopathy, characterized by ventricular dilatation and decreased systolic contraction, is twofold to threefold more common as a cause of heart failure than hypertrophic cardiomyopathy and costs several billion dollars annually. The idiopathic form occurring early in life, with a 75% mortality in 5 years, is a common reason for transplantation. It is estimated that at least 20% of cases are familial. METHODS AND RESULTS: A family of 46 members spanning four generations underwent history and physical examinations, echocardiographic analysis, and blood sampling for genotyping. Diagnostic criteria, detected by echocardiography, consisted of ventricular dimension of > or = 2.7 cm/m2 with an ejection fraction < or = 50% in the absence of other potential causes. DNA from all members was analyzed by polymerase chain reaction for amplification of short tandem-repeat polymorphic markers located every 10 cM throughout the human genome. Assuming a penetrance of 90%, linkage analysis was performed to map the responsible chromosomal locus. Linkage analysis, after 412 markers were analyzed, indicated the locus to be on chromosome 1q32, with a peak multipoint logarithm of the odds score at D1S414 of 6.37. CONCLUSIONS: The locus identified in this study for familial dilated cardiomyopathy, 1q32, is rich in candidate genes, such as MEF-2, renin, and helix loop helix DNA binding protein MYF-4. Identification of the genetic defect could provide insight into the molecular basis for the cardiac dilatory response in both familial and acquired disorders.
Authors: Jeanne L Theis; Katharine M Sharpe; Martha E Matsumoto; High Seng Chai; Asha A Nair; Jason D Theis; Mariza de Andrade; Eric D Wieben; Virginia V Michels; Timothy M Olson Journal: Circ Cardiovasc Genet Date: 2011-09-30
Authors: D Li; F Ahmad; M J Gardner; D Weilbaecher; R Hill; A Karibe; O Gonzalez; T Tapscott; G P Sharratt; L L Bachinski; R Roberts Journal: Am J Hum Genet Date: 2000-01 Impact factor: 11.025
Authors: P Skyllouriotis; M Skyllouriotis-Lazarou; S Natter; R Steiner; S Spitzauer; S Kapiotis; P Valent; A M Hirschl; S E Guber; G Laufer; G Wollenek; E Wolner; M Wimmer; R Valenta Journal: Clin Exp Immunol Date: 1999-02 Impact factor: 4.330
Authors: K R Bowles; R Gajarski; P Porter; V Goytia; L Bachinski; R Roberts; R Pignatelli; J A Towbin Journal: J Clin Invest Date: 1996-09-15 Impact factor: 14.808