Summary
To understand the molecular basis of familial hypertrophic cardiomyopathy (FHC) in the Chinese population, a family with FHC was investigated. Nineteen family members who were 16 years of age or older were examined by M-mode or two-dimensional echocardiography. Eight members were diagnosed to be affected echocardiographically or clinically. Lymphocytes isolated from 20 family members were successfully transformed into permanent lymphoblastoid cell lines by Epstein-Barr virus. Three genomic DNA probes (CRI-L436, CRI-L329, and pSC14) that were derived from chromosome 14q1 loci and demonstrated to be linked closely to FHC were used to probe this family. Using the techniques of restriction fragment length polymorphism (RFLP) and linkage analysis, the probe CRI-L436, which recognized locus D14S26, was found informative in this family. The lod scores were -2.0 at θ = 0.025 and -1.49 at θ = 0.05. Thus, there was no evidence of linkage between the locus D14S26 and the gene for FHC in the pedigree studied. In addition, polymerase chain reaction (PCR) amplification did not indicate a mutation on exon 13 of the β cardiac myosin heavy chain gene as previously reported. Our data suggest that FHC is a genetically heterogeneous disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ciro E, Nichols PF III, Maron BJ (1983) Heterogeneous morphological expression of genetically transmitted hypertrophic cardiomyopathy: two-dimensional echocardiographic analysis. Circulation 67:1227–1233
Cox DW, Brubacher MG, Siewertsen M, Benger JC, Barker DF, Vosberg H-P (1989) Linkage relations of polymorphic markers on chromosome 14. (10th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 5:A2695
Donis-Keller H, Green P, Helms C, et al (1987) A genetic linkage map of the human genome. Cell 51:319–337
Epstein N, Fananapazir L, Lin H, Maron BJ, Malvihill J, White R, Lalouel JM, Nienhuis A, Leppert M (1990) Genetic heterogeneity in hypertrophic cardiomyopathy: evidence that HCM maps to chromosome 2p. Circulation 81 (Suppl III):399
Feigenbaum H (1981) Echocardiography, 3rd edn. Lea & Febiger, Philadelphia, pp 119–139
Ferrans VJ, Morrow AG, Roberts WC (1972) Myocardial ultrastructure in idiopathic hypertrophic subaortic stenosis: a study of operatively excised left ventricular outflow tract muscle in 14 patients. Circulation 45:769–792
Geisterfer-Lowrance AAT, Kass S, Tanigawa G, Vosberg H-P, McKenna W, Seidman CE, Seidman JG (1990) A molecular basis for familial hypertrophic cardiomyopathy: a β cardiac myosin heavy chain gene missense mutation. Cell 62:999–1006
Greaves SC, Roche AH, Neutze JM, Whitlock RM, Veale AM (1987) Inheritance of hypertrophic cardiomyopathy: a cross sectional and M-mode echocardiographic study of 50 families. Br Heart J 58:259–266
Hejtmancik JF, Brink PA, Towbin J, Hill R, Brink L, Czemuszewicz GZ, Tapscott T, Trakhtenbroit A, Perryman B, Robert R (1991) Localization of the gene for familial hypertrophic cardiomyopathy to chromosome 14q1 in a diverse American population (abstract). J Am Coll Cardiol 17:165A
Jarcho JA, McKenna W, Pare JAP, Solomon SD, Holcombe RF, Dickie S, Levi T, Donis-Keller H, Seidman JG, Seidman CE (1989) Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1. N Engl J Med 321:1372–1378
Lichter P, Umeda PK, Levin JE, Vosberg H-P (1986) Partial characterization of the human β-myosin heavy chain gene which is expressed in heart and skeletal muscle. Eur J Biochem 160:419–426
Liew CC, Sole MJ, Yamaguchi, Takihara K, Kelam B, Anderson D, Lin L, Liew JC (1990) Complete sequence and organization of the human cardiac β-myosin heavy chain gene. Nucleic Acids Res 18:3647–3651
Maron BJ, Gottdiener JS, Epstein SE (1981) Patterns and significance of distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: a wide angle, two dimensional echocardiographic study of 125 patients. Am J Cardiol 48:418–427
Maron BJ, Nichols PF III, Pickle LW, Wesley YE, Mulvihill JJ (1984) Patterns of inheritance in hypertrophic cardiomyopathy: assessment by M-mode and two-dimensional echocardiography. Am J Cardiol 53:1087–1094
Neitzel H (1986) A routine method for the establishment of permanent growing lymphoblastoid cell lines. Hum Genet 73: 320–326
Nishi H, Kimura A, Sasaki M, Wakisaka A, Matsuyama K, Koga Y, Toshima H, Sasazuki T (1989) Localization of the gene for hypertrophic cardiomyopathy to chromosome 18q. Circulation 79 (Suppl II):457
Ott J (1967) A computer program for linkage analysis of general human pedigrees. Am J Hum Genet 28:528–529
Solomon SD, Geisterfer-Lowrance AAT, Vosberg H-P, Hiller G, Jarcho JA, Morton CC, McBride WO, Mitchell AL, Bale AE, McKenna WJ, Seidman JG, Seidman CE (1990a) 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 q11–12. Am J Hum Genet 47:389–394
Solomon SD, Jarcho JA, McKenna W, Geisterfer-Lowrance A, Germain R, Salerni R, Seidman JG, Seidman CE (1990b) Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease. J Clin Invest 86:993–999
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
Tanigawa G, Jarcho JA, Kass S, Solomon SD, Vosberg H-P, Seidman JG, Seidman CE (1990) A molecular basis for familial hypertrophic cardiomyopathy: an α/β cardiac myosin heavy chain hybrid gene. Cell 62:991–998
Wigle ED, Sasson Z, Henderson MA, Ruddy TO, Fulop J, Rakowski H, William WG (1985) Hypertrophic cardiomyopathy, the importance of the site and extent of hypertrophy: a review. Prog Cardiovasc Dis 28:1–83
Yamaguchi-Takihara K, Sole MJ, Liew JC, Ing D, Liew CC (1989) Characterization of human cardiac myosin heavy chain genes. Proc Natl Acad Sci USA 86:3504–3508
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ko, YL., Lien, WP., Chen, JJ. 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). https://doi.org/10.1007/BF00221945
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00221945