title: Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
abstract: OBJECTIVE
  We sought to explore the relationship between a Tcap gene (TCAP) abnormality and cardiomyopathy.
  
  
  BACKGROUND
  Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) cause severe heart failure and sudden death. Recent genetic investigations have revealed that mutations of genes encoding Z-disc components, including titin and muscle LIM protein (MLP), are the primary cause of both HCM and DCM. The Z-disc plays a role in establishing the mechanical coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP complex serving as a mechanical stretch sensor. Tcap interacts with the calsarcin, which tethers the calcineurin to the Z-disc.
  
  
  METHODS
  The TCAP was analyzed in 346 patients with HCM (236 familial and 110 sporadic cases) and 136 patients with DCM (34 familial and 102 sporadic cases). Two different in vitro qualitative assays-yeast two-hybrid and glutathion S-transferase pull-down competition-were performed in order to investigate functional changes in Tcap's interaction with MLP, titin, and calsarcin-1 caused by the identified mutations and a reported DCM-associated mutation, R87Q.
  
  
  RESULTS
  Two TCAP mutations, T137I and R153H, were found in patients with HCM, and another TCAP mutation, E132Q, was identified in a patient with DCM. It was demonstrated by the qualitative assays that the HCM-associated mutations augment the ability of Tcap to interact with titin and calsarcin-1, whereas the DCM-associated mutations impair the interaction of Tcap with MLP, titin, and calsarcin-1.
  
  
  CONCLUSIONS
  These observations suggest that the difference in clinical phenotype (HCM or DCM) may be correlated with the property of altered binding among the Z-disc components.
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, and Laboratory of Genome Diversity, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Hayashi
authors.forename: Takuro
authors.initials: T
authors.lastname: Arimura
authors.forename: Manatsu
authors.initials: M
authors.lastname: Itoh-Satoh
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ueda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hohda
authors.forename: Natsuko
authors.initials: N
authors.lastname: Inagaki
authors.forename: Megumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hisae
authors.initials: H
authors.lastname: Hori
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nishi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Koga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Bo Yoon
authors.initials: BY
authors.lastname: Choi
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Bae
authors.forename: Cheol Woon
authors.initials: CW
authors.lastname: You
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Han
authors.forename: Jeong Euy
authors.initials: JE
authors.lastname: Park
authors.forename: Ralph
authors.initials: R
authors.lastname: Knöll
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hoshijima
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
mesh_terms: D044466:Asian People / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D064211:Connectin; D017931:DNA Primers; D005978:Glutathione; D006801:Humans; D007723:Korea; D060588:LIM Domain Proteins; D009124:Muscle Proteins / Q000235:genetics*; D019683:Penetrance; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics; D016415:Sequence Alignment; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D064211:Connectin; D017931:DNA Primers; D005978:Glutathione; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D011494:Protein Kinases; D000099163:Myosin Binding Protein C; C577292:TCAP protein, human; C577285:TTN protein, human; C090114:cysteine and glycine-rich protein 3