Genetic Analysis of Familial Hypertrophic Cardiomyopathy
Primary Purpose
Cardiovascular Diseases, Heart Diseases, Myocardial Diseases
Status
Completed
Phase
Locations
Study Type
Observational
Intervention
Sponsored by
About this trial
This is an observational trial for Cardiovascular Diseases
Eligibility Criteria
No eligibility criteria
Sites / Locations
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00005251
First Posted
May 25, 2000
Last Updated
March 15, 2016
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00005251
Brief Title
Genetic Analysis of Familial Hypertrophic Cardiomyopathy
Study Type
Observational
2. Study Status
Record Verification Date
June 2000
Overall Recruitment Status
Completed
Study Start Date
January 1990 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 1995 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
5. Study Description
Brief Summary
To map the genetic defect responsible for familial hypertrophic cardiomyopathy.
Detailed Description
BACKGROUND:
Familial hypertrophic cardiomyopathy is a disease of heart muscle that is genetically transmitted as an autosomal dominant trait, with a high degree of penetrance. Affected individuals typically have asymmetric thickening of the interventricular septum often involving the adjacent left ventricular free wall. Histologically, myocardial cells are enlarged and muscle bundles are grossly disorganized, producing a whorled pattern. The physiologic consequence of this cardiomyopathy is diastolic dysfunction with impaired ventricular relaxation and elevated diastolic pressures in the heart and pulmonary vasculature. Patients can experience dyspnea, angina, palpitations, and syncope. Complications of the disease include atrial fibrillation, congestive heart failure, thromboembolism, and most importantly, sudden death.
DESIGN NARRATIVE:
The three kindreds studied included one in Iceland, one in the St. Lawrence region in Canada, and one in the Pittsburgh, Pennsylvania area. Pedigrees were established for the three kindreds. All family members were clinically evaluated by physical exam, electrocardiogram, and comprehensive M-mode and two-dimensional echocardiography. Lymphoblastoid cell lines were derived from all members of the three pedigrees. Restriction fragment length polymorphism analyses were used to identify a DNA probe that was linked to familial hypertrophic cardiomyopathy. Studies were conducted to determine if the familial hypertrophic cardiomyopathy locus was the same in all three kindreds and to identify the gene responsible.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Diseases, Heart Diseases, Myocardial Diseases, Cardiomyopathy, Hypertrophic
7. Study Design
10. Eligibility
Sex
Male
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
No eligibility criteria
12. IPD Sharing Statement
Citations:
PubMed Identifier
1430197
Citation
Watkins H, Thierfelder L, Hwang DS, McKenna W, Seidman JG, Seidman CE. Sporadic hypertrophic cardiomyopathy due to de novo myosin mutations. J Clin Invest. 1992 Nov;90(5):1666-71. doi: 10.1172/JCI116038.
Results Reference
background
PubMed Identifier
1739523
Citation
Watkins H, Seidman CE, MacRae C, Seidman JG, McKenna W. Progress in familial hypertrophic cardiomyopathy: molecular genetic analyses in the original family studied by Teare. Br Heart J. 1992 Jan;67(1):34-8. doi: 10.1136/hrt.67.1.34. No abstract available.
Results Reference
background
PubMed Identifier
1806760
Citation
Seidman CE, Seidman JG. Mutations in cardiac myosin heavy chain genes cause familial hypertrophic cardiomyopathy. Mol Biol Med. 1991 Apr;8(2):159-66.
Results Reference
background
PubMed Identifier
1975599
Citation
Solomon SD, Jarcho JA, McKenna W, Geisterfer-Lowrance A, Germain R, Salerni R, Seidman JG, Seidman CE. Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease. J Clin Invest. 1990 Sep;86(3):993-9. doi: 10.1172/JCI114802.
Results Reference
background
PubMed Identifier
1975517
Citation
Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, Seidman JG. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell. 1990 Sep 7;62(5):999-1006. doi: 10.1016/0092-8674(90)90274-i.
Results Reference
background
PubMed Identifier
1975475
Citation
Solomon SD, Geisterfer-Lowrance AA, Vosberg HP, Hiller G, Jarcho JA, Morton CC, McBride WO, Mitchell AL, Bale AE, McKenna WJ, et al. A locus for familial hypertrophic cardiomyopathy is closely linked to the cardiac myosin heavy chain genes, CRI-L436, and CRI-L329 on chromosome 14 at q11-q12. Am J Hum Genet. 1990 Sep;47(3):389-94.
Results Reference
background
PubMed Identifier
2144212
Citation
Tanigawa G, Jarcho JA, Kass S, Solomon SD, Vosberg HP, Seidman JG, Seidman CE. A molecular basis for familial hypertrophic cardiomyopathy: an alpha/beta cardiac myosin heavy chain hybrid gene. Cell. 1990 Sep 7;62(5):991-8. doi: 10.1016/0092-8674(90)90273-h.
Results Reference
background
PubMed Identifier
7657806
Citation
Knowlton KU, Rockman HA, Itani M, Vovan A, Seidman CE, Chien KR. Divergent pathways mediate the induction of ANF transgenes in neonatal and hypertrophic ventricular myocardium. J Clin Invest. 1995 Sep;96(3):1311-8. doi: 10.1172/JCI118166.
Results Reference
background
PubMed Identifier
7981753
Citation
Watkins H, MacRae C, Thierfelder L, Chou YH, Frenneaux M, McKenna W, Seidman JG, Seidman CE. A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3. Nat Genet. 1993 Apr;3(4):333-7. doi: 10.1038/ng0493-333.
Results Reference
background
PubMed Identifier
8205619
Citation
Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell. 1994 Jun 3;77(5):701-12. doi: 10.1016/0092-8674(94)90054-x.
Results Reference
background
PubMed Identifier
8282798
Citation
Anan R, Greve G, Thierfelder L, Watkins H, McKenna WJ, Solomon S, Vecchio C, Shono H, Nakao S, Tanaka H, et al. Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. J Clin Invest. 1994 Jan;93(1):280-5. doi: 10.1172/JCI116957.
Results Reference
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PubMed Identifier
8250038
Citation
Watkins H, Thierfelder L, Anan R, Jarcho J, Matsumori A, McKenna W, Seidman JG, Seidman CE. Independent origin of identical beta cardiac myosin heavy-chain mutations in hypertrophic cardiomyopathy. Am J Hum Genet. 1993 Dec;53(6):1180-5.
Results Reference
background
PubMed Identifier
8335820
Citation
Solomon SD, Wolff S, Watkins H, Ridker PM, Come P, McKenna WJ, Seidman CE, Lee RT. Left ventricular hypertrophy and morphology in familial hypertrophic cardiomyopathy associated with mutations of the beta-myosin heavy chain gene. J Am Coll Cardiol. 1993 Aug;22(2):498-505. doi: 10.1016/0735-1097(93)90055-6.
Results Reference
background
PubMed Identifier
1552912
Citation
Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992 Apr 23;326(17):1108-14. doi: 10.1056/NEJM199204233261703.
Results Reference
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Genetic Analysis of Familial Hypertrophic Cardiomyopathy
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