%0 Journal Article %T A negative screen for mutations in calstabin 1 and 2 genes in patients with dilated cardiomyopathy %A Diogo G Biagi %A Jos¨¦ G Mill %A Alfredo J Mansur %A Jos¨¦ E Krieger %A Alexandre C Pereira %J Journal of Negative Results in BioMedicine %D 2012 %I BioMed Central %R 10.1186/1477-5751-11-4 %X We tested the hypothesis that calstabins mutations may cause dilated cardiomyopathy in humans screening 186 patients with idiopathic dilated cardiomyopathy for genetic alterations in calstabins 1 and 2 genes (FKBP12 and FKBP12.6). No missense variant was found. Five no-coding variations were found but not related to the disease.These data corroborate other studies suggesting that mutations in FKBP12 and FKBP12.6 genes are not commonly related to cardiac diseases.Ryanodine receptors (RyRs) are the main proteins in the sarcoplasmic reticulum (SR) calcium-release channel and are modulated by other proteins in the regulation of muscle excitation-contraction coupling[1]. Calstabins 1 and 2 (FKBP12 and FKBP12.6 genes, respectively) bind both RyR1 (skeletal form) and RyR2 (cardiac form) although calstabin1 has higher affinity to RyR1, and calstabin2 to RyR2 [2-4]. The RyR-calstabin interaction occurs to stabilize the RyR channel in the closed state, but its specific amino acids binding site is still controversial [5-7]. Although, calstabin1 deficient mice display normal skeletal muscle phenotype, they have severe Dilated Cardiomyopathy (DCM) and ventricular septal defects [8]. Mice with a disruption in calstabin2 display hypertrophic cardiomyopathy only in males. However, both males and females present a similar dysregulation of Ca2+ release [9].Disease-causing mutations in RyRs 1 and 2 affecting the interaction with calstabins were described as leading to different phenotypes [1]. Wehrens and colleagues reported RyR2 mutations which decrease the affinity of RyR2 with calstabin2 in patients with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) [7]. However, no mutation in calstabin2 seemed to be involved with the disease [10]. The association of calstabins with heart disease was also tested in a familial Hypertrophic Cardiomyopathy cohort, and no mutation was found in all 252 patients [11]. Recently, Oyama and colleagues have reported an increased expression of %K Genetic screening %K Calstabin %K FKBP12 %K FKBP12.6 %U http://www.jnrbm.com/content/11/1/4