title: Desmin A213V substitution represents a rare polymorphism but not a mutation and is more prevalent in patients with heart dilation of various origins.
abstract: Several desmin mutations have been described in patients with cardiomyopathies and distal myopathies. Among them, A213V substitution has been associated with three completely different clinical phenotypes: restrictive cardiomyopathy, dilated cardiomyopathy and isolated distal myopathy. However, the identification of this substitution also in control subjects has highlighted the question if the A213V shift represents a conditional mutation, giving rise to cardiomyopathy only in the presence of other predisposing factors. The aim of the present work was to study the potential role of this substitution in predisposing to heart dilation. Methods and results. We screened 108 patients with heart dilation due to ischemic heart disease, alcoholic cardiomyopathy or viral myocarditis, and 300 healthy controls for the presence of A213V substitution by direct sequencing and confirmed the results by site-specific restriction. In the control group A213V substitution was identified in 3 out of 300 patients, representing a rare polymorphism with a frequency of approximately 1%, which corresponds to the earlier reported frequency. In the study group A213V substitution was found in 5 out of 108 cases, corresponding to approximately 4.6% (p < 0.035). Therefore we conclude that A213V desmin substitution represents a conditional mutation, i.e. a rare polymorphism that plays a role as a predisposing factor resulting in maladaptive heart remodelling in the presence of other pathological factors.
authors.affiliation: Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden. anna.kostareva@ki.se
authors.forename: A
authors.initials: A
authors.lastname: Kostareva
authors.forename: G
authors.initials: G
authors.lastname: Sjoberg
authors.forename: A
authors.initials: A
authors.lastname: Gudkova
authors.forename: N
authors.initials: N
authors.lastname: Smolina
authors.forename: E
authors.initials: E
authors.lastname: Semernin
authors.forename: E
authors.initials: E
authors.lastname: Shlyakhto
authors.forename: T
authors.initials: T
authors.lastname: Sejersen
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D003893:Desmin / Q000235:genetics*; D049310:Distal Myopathies / Q000150:complications / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D003893:Desmin