TY - JOUR
T1 - Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy
AU - Chiu, Christine
AU - Tebo, Molly
AU - Ingles, Jodie
AU - Yeates, Laura
AU - Arthur, Jonathan W.
AU - Lind, Joanne M.
AU - Semsarian, Christopher
PY - 2007/9
Y1 - 2007/9
N2 - Genes encoding Ca2+ regulatory proteins responsible for Ca2+ homeostasis have been suggested as possible candidates for FHC. Mutations in sarcomere genes account for approximately 50% of all FHC cases indicating other genes, including those involved in Ca2+ handling, may account for the remainder. The aim of this study was to identify causative mutations in genes involved in Ca2+ regulation in patients with familial hypertrophic cardiomyopathy (FHC). An Australian cohort of 252 unrelated familial hypertrophic cardiomyopathy patients were screened for mutations in the Ca2+ regulatory genes, sorcin (SRI), calstabin (FKBP1B), calsequestrin (CASQ2), phospholamban (PLN), sarcolipin (SLN), calreticulin (CALR3) and calmodulin (CALM). A total of 17 exonic DNA variants were identified in the 7 Ca2+ regulatory genes studied, of which 4 were considered of pathogenic significance. Two novel mutations in the CALR3 gene were identified (Lys82Arg, Arg73Gln) and one truncation mutation in the PLN gene (Leu39Ter). A variant was also identified in the CASQ2 gene (Asp63Glu). These four variants were all novel, resulted in changes in conserved amino acids and were not identified in a normal population. In conclusion, mutations in Ca2+ handling genes are an infrequent but important cause of FHC. DNA variants in Ca2+ genes may also be involved as modifying factors in phenotype development. Further evaluation of the role of defects in Ca2+ regulation will shed light on the molecular pathogenesis of FHC.
AB - Genes encoding Ca2+ regulatory proteins responsible for Ca2+ homeostasis have been suggested as possible candidates for FHC. Mutations in sarcomere genes account for approximately 50% of all FHC cases indicating other genes, including those involved in Ca2+ handling, may account for the remainder. The aim of this study was to identify causative mutations in genes involved in Ca2+ regulation in patients with familial hypertrophic cardiomyopathy (FHC). An Australian cohort of 252 unrelated familial hypertrophic cardiomyopathy patients were screened for mutations in the Ca2+ regulatory genes, sorcin (SRI), calstabin (FKBP1B), calsequestrin (CASQ2), phospholamban (PLN), sarcolipin (SLN), calreticulin (CALR3) and calmodulin (CALM). A total of 17 exonic DNA variants were identified in the 7 Ca2+ regulatory genes studied, of which 4 were considered of pathogenic significance. Two novel mutations in the CALR3 gene were identified (Lys82Arg, Arg73Gln) and one truncation mutation in the PLN gene (Leu39Ter). A variant was also identified in the CASQ2 gene (Asp63Glu). These four variants were all novel, resulted in changes in conserved amino acids and were not identified in a normal population. In conclusion, mutations in Ca2+ handling genes are an infrequent but important cause of FHC. DNA variants in Ca2+ genes may also be involved as modifying factors in phenotype development. Further evaluation of the role of defects in Ca2+ regulation will shed light on the molecular pathogenesis of FHC.
KW - Calcium
KW - Calreticulin
KW - Genes
KW - Hypertrophic cardiomyopathy
KW - Phospholamban
UR - http://www.scopus.com/inward/record.url?scp=34548118345&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2007.06.009
DO - 10.1016/j.yjmcc.2007.06.009
M3 - Article
C2 - 17655857
AN - SCOPUS:34548118345
VL - 43
SP - 337
EP - 343
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 3
ER -