CSRP3 – Dilated Cardiomyopathy

CSRP3 encodes muscle LIM protein (MLP), a Z-disc component implicated in cardiomyocyte mechano‐sensory signaling. Autosomal-dominant CSRP3 variants have been reported in dilated cardiomyopathy (DCM) cohorts. Resequencing of 73 unrelated DCM probands identified two rare missense variants (c.148G>A (p.Ala50Thr) and c.206A>G (p.Lys69Arg)) in CSRP3 using a custom DCM CardioChip (PMID:20474083). In a separate study of 100 idiopathic DCM cases, one synonymous CSRP3 variant (c.96G>A (p.Lys32=)) was identified and predicted to alter mRNA structure and splicing regulatory elements (PMID:36877346). No familial segregation data are available for these variants, and case–control analyses did not firmly establish pathogenicity.

Functional studies support a role for CSRP3 deficiency in DCM. A zebrafish gene-trap model disrupting csrp3 exhibits excessive ventricular trabeculation—mirroring human DCM pathology—and impaired cardiomyocyte proliferation during heart regeneration (PMID:38556571). Human embryonic stem cell-derived cardiomyocytes lacking CSRP3 develop early hypertrophic changes that progress to heart failure phenotypes with mitochondrial damage and calcium‐handling defects, which are rescued by verapamil (PMID:31406109).

References

• Genetics in medicine • 2010 • A novel custom resequencing array for dilated cardiomyopathy. PMID:20474083
• Molecular biology reports • 2023 • Identification and in silico characterization of CSRP3 synonymous variants in dilated cardiomyopathy. PMID:36877346
• Cellular and molecular life sciences : CMLS • 2024 • A novel gene-trap line reveals the dynamic patterns and essential roles of cysteine and glycine-rich protein 3 in zebrafish heart development and regeneration. PMID:38556571
• Cell death & disease • 2019 • MLP-deficient human pluripotent stem cell derived cardiomyocytes develop hypertrophic cardiomyopathy and heart failure phenotypes due to abnormal calcium handling. PMID:31406109

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