Original ArticleSarcomeric Genotyping in Hypertrophic Cardiomyopathy
Section snippets
MATERIAL AND METHODS
Review of PubMed and MEDLINE search results revealed several studies published in the English language of large groups of unrelated patients with HCM who had been genotyped for sarcomeric mutations. Data published from November 1998 through November 2004 were gathered and compared from unrelated study population genotyping studies from the Mayo Clinic (Rochester, Minn),11, 22, 23, 24, 25 Harvard Medical School (Boston, Mass),26 France,10 Germany,27 Sweden,28 Spain,29 and Finland.30, 31, 32, 33
Study Population Analyses
Table 1 summarizes the clinical characteristics of each study population analyzed, except for the Harvard study population for whom data were not available. Study population size, genes screened, and methods used are summarized in Table 2. Note that the Mayo Clinic and French studies reported complete analysis of each of the 8 sarcomeric genes; the Harvard and Swedish studies reported complete analysis of all but MYH7, which was analyzed in part; and the German, Finnish, and Spanish studies
Study Population Analyses
Because each study population is clinically unique, extrapolations from any individual study population to the general HCM population must be made judiciously. Specifically, patients from tertiary referral centers for HCM may not be representative of the general HCM population. Of the 2 largest study populations, the Mayo Clinic HCM study population is overrepresented by patients treated surgically for left ventricular outflow obstruction, and the French study population overwhelmingly
CONCLUSIONS
Several conclusions can be drawn pertaining to the cardiac sarcomere gene screen in the evaluation of HCM. First, although HCM has been coined the “disease of the sarcomere,” more than half of unrelated patients will have no identifiable HCM-associated variant among the currently known sarcomere genes implicated in the pathogenesis of HCM. Novel genetic and/or environmental causes of this disease must be elucidated to determine the pathogenic mechanisms at work in patients with nonsarcomeric
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This study was supported by a Mayo Foundation clinical research award to Dr Ackerman. Dr Ackerman is an established investigator of the American Heart Association.