Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy

Christine Chiu, Molly Tebo, Jodie Ingles, Laura Yeates, Jonathan W. Arthur, Joanne M. Lind, Christopher Semsarian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)337-343
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Issue number3
Publication statusPublished - Sept 2007
Externally publishedYes


  • Calcium
  • Calreticulin
  • Genes
  • Hypertrophic cardiomyopathy
  • Phospholamban


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