Mutations in PDLIM3 and MYOZ1 encoding myocyte Z line proteins are infrequently found in idiopathic dilated cardiomyopathy

Dilated cardiomyopathy (DCM), characterized by ventricular dilation and decreased systolic function, is estimated to be of genetic origin in up to 50% of cases. In the present study, we investigated the role of two genes, encoding the Z line proteins PDZ and LIM domain protein 3 (PDLIM3) and myozenin-1 (MYOZ1), in the etiology of DCM. The coding regions of PDLIM3 and MYOZ1 were first amplified from the genomic DNA of 185 unrelated DCM patients by polymerase chain reaction (PCR), followed by denaturing high-performance liquid chromatography (DHPLC) analysis. The samples that exhibited abnormal peaks on DHPLC were re-amplified, purified and sequenced using a Big-Dye Terminator cycle sequencing system. Interestingly, a 2-bp insertion (178insCA) in exon 2 of PDLIM3 was identified in one patient who presented with DCM during pregnancy and died a year later awaiting heart transplant. No other significant mutations were found in either PDLIM3 or MYOZ1. The mutation probably resulted in an unstable protein, since no exogenous protein could be detected in transfected murine myoblastoid cells by immunohistochemical or Western blot analyses. We conclude that mutations in PDLIM3 and MYOZ1, encoding myocyte Z line proteins, do not play any significant role in the genetic etiology of idiopathic DCM. The exact mechanism by which the mutation identified in the present study is linked to DCM phenotype remains unknown. The hemodynamic burden of pregnancy and/or other genetic or environmental factors could have precipitated heart failure symptoms in an individual with defective myocardial cytoarchitecture.