Supplementary Materials

The PDF file includes:

  • Fig. S1. Primary cilia are detected in human mitral valves during development.
  • Fig. S2. Primary cilia are located in areas rich in versican.
  • Fig. S3. Loss of primary cilia has no effect on cell proliferation.
  • Fig. S4. Loss of primary cilia results in decreased cell density.
  • Fig. S5. RNA-seq analyses correlate loss of cilia with ECM gene activation.
  • Fig. S6. Loss of primary cilia results in increased collagen I expression in mitral valves.
  • Fig. S7. Cilia length is decreased in mouse models associated with MVP.
  • Fig. S8. MVP of proband from family with chromosome 13 mutation is observed through echocardiographic assessment.
  • Fig. S9. DZIP1 is expressed at the base of primary cilia in the murine mitral valve.
  • Fig. S10. Dzip1S14R/+ KI MVP mouse models were generated through CRISPR-Cas9.
  • Fig. S11. GO analyses of RNA-seq datasets reveal changes in ECM synthesis.
  • Fig. S12. Mutated DZIP1 is unstable.
  • Fig. S13. Loss of Dzip1 causes developmental defects and subsequent MVP in the adult.
  • Fig. S14. Echocardiography of Dzip1 conditional knockout mitral leaflets shows MVP.
  • Table S1. WES to identify additional DZIP1 variants.
  • Table S2. Echocardiographic analyses of Dzip1S14R/+ and control mice.
  • Table S3. Echocardiographic analyses of Dzip1 conditional heterozygote and homozygote mice.
  • Legends for movies S1 to S10

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Other Supplementary Material for this manuscript includes the following:

  • Movie S1 (.mp4 format). 3D reconstruction of primary cilia in E13.5 murine anterior mitral leaflets.
  • Movie S2 (.mov format). 3D reconstruction of primary cilia in E15.5 murine anterior mitral leaflets.
  • Movie S3 (.mp4 format). 3D reconstruction of primary cilia in 10-week-old human fetal anterior mitral leaflets.
  • Movie S4 (.mov format). EM tomography showing the presence of the axoneme and basal body.
  • Movie S5 (.mov format). EM tomography showing a compilation of transmission electron microscopy slices and renderings of the microtubule triplets that comprise the mother centriole/basal body.
  • Movie S6 (.mp4 format). 3D reconstruction of primary cilia and versican in P0 anterior mitral leaflets.
  • Movie S7 (.mp4 format). 3D reconstruction of primary cilia and collagen IαI in P0 anterior mitral leaflets.
  • Movie S8 (.mp4 format). 3D reconstruction of DZIP1 protein expression in an E13.5 AV cushion mesenchymal cell.
  • Movie S9 (.mp4 format). Echocardiography: Parasternal long-axis view of Dzip1S14R/+ mitral leaflet.
  • Movie S10 (.mov format). Echocardiography: Parasternal long-axis view of Dzip1 conditional knockout mice.
  • Data file S1 (Microsoft Excel format). Cilia length during development.
  • Data file S2 (Microsoft Excel format). Correlation of cilia with the type of ECM produced in the valve.
  • Data file S3 (Microsoft Excel format). Morphometrics of valve geometry in Ift88-deficient mitral valves compared to controls at P0.
  • Data file S4 (Microsoft Excel format). Cell proliferation in Ift88-deficient mitral valves compared to controls at P0.
  • Data file S5 (Microsoft Excel format). Decreased cell density Ift88-deficient valves.
  • Data file S6 (Microsoft Excel format). Increased collagen production in Ift88-deficient valves.
  • Data file S7 (Microsoft Excel format). List of cilia genes, gene function, and disease association used in GWAS analyses.
  • Data file S8 (Microsoft Excel format). Details about cilia gene set enrichment results using i-GSEA4GWAS.
  • Data file S9 (Microsoft Excel format). Reduced cilia lengths in Dchs1- and Flna-deficient mitral valves.
  • Data file S10 (Microsoft Excel format). Morphometrics of Dzip1S14R/+ mitral valves at P0 compared to controls.
  • Data file S11 (Microsoft Excel format). Shortened cilia length in Dzip1S14R/+ mitral valves at P0 compared to controls.
  • Data file S12 (Microsoft Excel format). Differentially expressed gene comparison.
  • Data file S13 (Microsoft Excel format). Reduced protein half-life of DZIP1S24R variant.
  • Data file S14 (Microsoft Excel format). Reduced cilia length in Dzip1 conditional knockout mice.