Abstract
Familial hypertrophic cardiomyopathy (FHC) is a cardiac disorder transmitted as an autosomal dominant trait. FHC has been shown to be genetically heterogeneous with less than 50% of published pedigrees being associated with mutations in the p myosin heavy chain (β–MHC) gene on chromosome 14q11–q12. A second locus has recently been reported on chromosome 1. We examined the segregation of microsatellite markers in a French pedigree for which the disease is not linked to β–MHC gene. We found significant linkage of the disease locus to several (CA)n repeats located on chromosome 11 (lod scores between +3.3 and +4.98). The data suggest the localization of the novel FHC gene in a region spanning 17 centiMorgans.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Maron, B.J., Nichols, P.F., Pickle, L.W., Wesley, Y.E. & Mulvihill, J.J. Patterns of Inheritance in Hypertrophic Cardiomyopathy. Assessment by M-Mode and Two-Dimensional Echocardiography. Am. J. Cardiol. 53, 1087–1094 (1984).
Maron, B.J. & Ferrans, V.J., Ultrastural Features of Hypertrophied Human Ventricular Myocardium. Prog. Cardiovasc. Dis. 21, 207–238 (1978).
Jarcho, J.A. et al. Mapping a Gene for Familial Hypertrophic Cardiomyopathy to Chromosome 14ql. New Engl. J. Med. 321, 1372–1378 (1989).
Solomon, S.D. 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. 47, 389–394 (1990).
Solomon, S.D. et al. Familial Hypertrophic Cardiomyopathy is a Genetically Heterogeneous Disease. J. clin. Invest. 86, 993–999 (1990).
Hejtmancik, J.F. et al. Localization of Gene for Familial Hypertrophic Cardiomyopathy to chromosome 14q1 in a diverse US population. Circulation 83, 1592–1597 (1991).
Epstein, N.D. et al. Evidence of Genetic Heterogeneity in Five Kindreds with Familial Hypertrophic Cardiomyopathy. Circulation 85, 635–647 (1992).
Geisterfer-Lowrance, A.A.T. et al. A Molecular Basis for Familial Hypertrophic Cardiomyopathy: a β Cardiac Myosin Heavy Chain Gene Missense Mutation. Cell 62, 999–1006 (1990).
Tanigawa, G. et al. A Molecular Basis for Familial Hypertrophic Cardiomyopathy: an α/β Cardiac Myosin Heavy Chain Hybrid Gene. Cell 62, 991–998 (1990).
Epstein, N.D., Conn, G.M., Cyran, F. & Fananapazir, L. Differences in Clinical Expression of Hypertrophic Cardiomyopathy Associated With Two Distinct Mutations in the β-Myosin Heavy Chain Gene: A 908Leu→Val Mutation and a 403Arg→Gin Mutation. Circulation 86, 345–352 (1992).
Watkins, H. et al. Characteristics and Prognostic Implications of Myosin Missense Mutations in Familial Hypertrophic Cardiomyopathy. New Engl. J. Med. 326, 1106–1114 (1992).
Mares, A. et al. Genetic Screening of 75 Families with Hypertrophic Cardiomyopathy Show Missense Mutations the Most Common Genetic Defect. Circulation 86, 1–228 (1992).
Nishi, H., Kimura, A., Harada, H., Toshima, H. & Sasazaki, T., Novell Missense Mutation in Cardiac b Myosin Heavy Chain Gene Found in a Japanese Patient with Hypertrophic Cardiomyopathy. Biochem. Biophys. Res. Commun. 188, 379–387 (1992).
Fananapazir, L., Dalakas, M., Cyran, F., Conn, G. & Epstein, N., Disease is Present in Hypertrophic Cardiomyopathy with Distinct Mutations in the Beta Myosin Heavy Chain Gene. Circulation 86, 1–229 (1992).
Cuda, G., Fananapazir, L., Epstein, N. & Sellers, J., Abnormal Myosin In-Vitro Motility Activity in Two Hypertrophic Cardiomyopathy Kindreds with Distinct Cardiac Beta Myosin Heavy Chain Gene Mutations. Circulation 86, 1–229 (1992).
Marian, A.J. et al. Detection of a New Mutation in the β-Myosin Heavy Chain Gene in an Individual With Hypertrophic Cardiomyopathy. J. clin. Invest. 90, 2156–2174 (1992).
Harada, H. et al. Genetic Analysis of Hypertrophic Cardiomyopathy. Circulation 86, 1–591 (1992).
Hirschfield, W., Hunter, J., Corfield, V., Weich, H.F.H. & Brink, P. Choromosome 14 Linkage Studies in a South African Families with Hypertrophic Cardiomyopathy. Eur. Heart J. 13, 32 (1992).
Ko, Y.L. et al. No Evidence for Linkage of Familial Hypertrophic Cardiomyopathy and Chromosome 14q1 Locus D14S26 in a Chinese Family: Evidence for Genetic Heterogeneity. Hum. Genet. 89, 597–601 (1992).
Schwartz, K. et al. Exclusion of Cardiac Myosin Heavy Chain and Actin Gene Involvement in Hypertrophic Cardiomyopathy of Several French Families. Circ Res. 71, 3–8 (1992).
Dufour, C. et al. Exclusion of genes coding for proteins of the cytoskeleton and the extracellular matrix in familial hypertrophic cardiomyopathy using a candidate gene approach. C.R. Acad. Sci. 316, (in the press).
Weissenbach, J. et al. A Second-Generation Linkage Map of the Human Genome. Nature 359, 794–801 (1992).
NIH/CEPH Collaborative Group. A Comprehensive Genetic Linkage Map of the Human Genome. Science 258, 67–86 (1992).
Watkins, H. et al. A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3. Nature Genet. 3, 333–337 (1993).
Richards, E.J. Preparation and Analysis of DNA. in Current Protocol in Molecular Biology (eds Ausubel, F.M., Brent, R. & Kingston, R.E.) 1, 2.0.1–2.10.3 (Wiley, New York, 1987).
Vignal, A. et al. Nonradioactive Multiplex Procedure for Genotyping of Microsatellite Markers in Methods in Molecular Genetics: Chromosome and Gene Analysis 1 (ed. K.W. Adolph), 211–221 (Academic Press, Orlando, Florida, 1993).
Lathrop, G.M. & Lalouel, J.M., Calculations of Lod scores and Genetic Risks on Small Computers. Am. J. hum. Genet. 36, 460–465 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carrier, L., Hengstenberg, C., Beckmann, J. et al. Mapping of a novel gene for familial hypertrophic cardiomyopathy to chromosome 11. Nat Genet 4, 311–313 (1993). https://doi.org/10.1038/ng0793-311
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0793-311
This article is cited by
-
Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs
Experimental & Molecular Medicine (2023)
-
Predictive genomic tools in disease stratification and targeted prevention: a recent update in personalized therapy advancements
EPMA Journal (2022)
-
Analysis of rare genetic variation underlying cardiometabolic diseases and traits among 200,000 individuals in the UK Biobank
Nature Genetics (2022)
-
Personalized medicine in cardiovascular disease: review of literature
Journal of Diabetes & Metabolic Disorders (2021)
-
Genetic, clinical, molecular, and pathogenic aspects of the South Asian–specific polymorphic MYBPC3Δ25bp variant
Biophysical Reviews (2020)