Dilated cardiomyopathy and the desmin gene.

Abstract

To the Editor: Li et al1 report a mutation screening study of actin and desmin genes in 44 probands with familial dilated cardiomyopathy (DCM) and conclude that a mutation of the desmin gene can cause DCM. We believe that the genetic data are not yet sufficient to justify this conclusion. Attempts to find genes for autosomal dominant DCM by linkage analysis have been frustrating; although 6 chromosomal loci have been mapped, none of these linkages have yet led to disease-gene identification. Not surprisingly, investigators have turned to direct candidate gene analysis. However, in forgoing linkage analysis, one of the pillars of evidence supporting a real association is removed. Other criteria for assessing a causal effect are that the DNA variant in the affected individuals is not present in a large number of normal controls, that the predicted change in the encoded protein is significant, and that mutations in the same gene are found in more than 1 affected family. Such observations have been sufficient to propose a causal role for missense mutations in cardiac actin in DCM.2 However, without evidence of cosegregation (linkage) or an observed biological effect, some uncertainty remains, and actin mutations have not yet been found in other DCM series. …