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PDLIM3 encodes the PDZ and LIM domain protein 3, a myocyte Z line component essential for sarcomere integrity. Dilated cardiomyopathy (DCM), defined by ventricular dilation and systolic dysfunction, is genetically heterogeneous with up to 50% familial etiology. In a screen of 185 unrelated individuals with idiopathic DCM, a single heterozygous 2-bp insertion, c.177_178dup (p.Met60fs), was identified in exon 2 of PDLIM3 and absent in controls (PMID:17254821). Functional studies in murine myoblastoid cells expressing the mutant allele failed to detect exogenous protein by immunohistochemistry or Western blot, indicating an unstable truncation product. No additional PDLIM3 variants or familial segregation data were described. These findings have not been replicated in independent cohorts, and no recurrent or founder alleles have emerged. Thus, the current evidence for Dilated cardiomyopathy remains limited, highlighting the need for further genetic and functional validation before clinical application.
Gene–Disease AssociationLimitedOne proband with frameshift c.177_178dup (p.Met60fs); no segregation or replication ([PMID:17254821]). Genetic EvidenceLimitedSingle loss-of-function variant in one proband; no familial segregation; inheritance unconfirmed. Functional EvidenceLimitedIn vitro expression assays show absence of mutant protein; no in vivo or rescue data. |