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(Circulation. 1995;91:2865-2867.)
© 1995 American Heart Association, Inc.

Articles

Familial Hypertrophic Cardiomyopathy

Nonsense Versus Missense Mutations

Ketty Schwartz, PhD

From the INSERM UR 153, Paris, France.

Correspondence to Ketty Schwartz, INSERM UR 153, Pavillon Rambuteau, Groupe Hospitalier Pitié-Salpêtrière, 47, Boulevard de l'Hôpital, Paris Cedex 13, France.

Key Words: hypertrophic cardiomyopathy • missense mutations • nonsense mutations • myosin heavy chain • Editorials

	Introduction

 
During the last 5 years familial hypertrophic cardiomyopathy (FHC) has become the paradigm of inherited cardiac disorders analyzed at the molecular and genetic levels. The history of this pathology is rather unusual. Observations of myocardial diseases that can reasonably be interpreted as hypertrophic cardiomyopathy were made in the middle of the last century at the Hospital de la Salpêtrière in Paris by A. Vulpian, who called what he saw at the macroscopic level "retrecissement de l'orifice ventriculo-aortique."¹ One of his pupils, H. Liouville, even predicted 1 year later that this pathology would have a great clinical impact once physicians began to pay sufficient attention to it.² This took 1 century: it was only in the late 1950s that the unique clinical features of hypertrophic cardiomyopathy were systematically described.³ The first large pedigree was reported in 1960,⁴ the first disease locus in 1989,⁵ and the first disease gene in 1990.⁶ Since then, an unexpected genetic heterogeneity has been found. Four disease loci exist: CMH1 on chromosome 14q11-12,⁵ CMH2 on chromosome 1q3,⁷ CMH3 on chromosome 15q2,⁸ and CMH4 on chromosome 11p13-q13.⁹ Moreover, we have evidence that a fifth locus exists.¹⁰ Three genes have been identified within these loci, and it was a surprise to find that they encode cardiac sarcomeric proteins, ß–myosin heavy chain,⁶ cardiac troponin T, and -tropomyosin.¹¹ Indeed, none of the previous hypotheses of the pathophysiological mechanisms of the disease would have predicted that among the possible molecular bases there could be a defect in a contractile protein; nevertheless, certain . . . [Full Text of this Article]

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