New insights into the pathogenesis of pseudoxanthoma elasticum and related soft tissue calcification disorders by identifying genetic interactions and modifiers

Frontiers in Genetics

Volumn 4, Issue JUN, 2013, Pages

  Hendig, Doris ^a   Knabbe, Cornelius ^a   Götting, Christian ^a  

^a RUHR UNIVERSITY BOCHUM   (Germany)

Author keywords

Calcification; Genetic interaction; Genetic modifier; Mineralization; PXE; Rare disease

Indexed keywords

EID: 84883542427     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2013.00114     Document Type: Short Survey

References (63)

1. Aherrahrou, Z., Axtner, S. B., Kaczmarek, P. M., Jurat, A., Korff, S., Doehring, L. C., et al. (2004). A locus on chromosome 7 determines dramatic up-regulation of osteopontin in dystrophic cardiac calcification in mice. Am. J. Pathol. 164, 1379-1387. doi: 10.1016/S0002-9440(10)63224-5
2. Annovazzi, L., Viglio, S., Gheduzzi, D., Pasquali-Ronchetti, I., Zanone, C., Cetta, G., et al. (2004). High levels of desmosines in urine and plasma of patients with pseudoxanthoma elasticum. Eur. J. Clin. Invest. 34, 156-164. doi: 10.1111/j.1365-2362.2004.01306.x
3. Antonarakis, S. E., and Beckmann, J. S. (2006). Mendelian disorders deserve more attention. Nat. Rev. Genet. 7, 277-282. doi: 10.1038/nrg1826
4. Baccarani-Contri, M., Vincenzi, D., Cicchetti, F., Mori, G., and Pasquali-Ronchetti, I. (1994). Immunochemical identification of abnormal constituents in the dermis of pseudoxanthoma elasticum patients. Eur. J. Histochem. 38, 111-123.
5. Bergen, A. A., Plomp, A. S., Schuurman, E. J., Terry, S., Breuning, M., Dauwerse, H., et al. (2000). Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat. Genet. 25, 228-231. doi: 10.1038/76109
6. Berndt, A., Li, Q., Potter, C. S., Liang, Y., Silva, K. A., Kennedy, V., et al. (2012). A single-nucleotide polymorphism in the Abcc6 gene associates with connective tissue mineralization in mice similar to targeted models for pseudoxanthoma elasticum. J. Invest. Dermatol. 133, 833-836. doi: 10.1038/jid.2012.340
7. Costrop, L. M., Vanakker, O. O., Van Laer, L., Le Saux, O., Martin, L., Chassaing, N., et al. (2010). Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region. J. Hum. Genet. 55, 112-117. doi: 10.1038/jhg.2009.132
8. Cutting, G. R. (2005). Modifier genetics: cystic fibrosis. Annu. Rev. Genomics Hum. Genet. 6, 237-260. doi: 10.1146/annurev.genom.6.080604.162254
9. D'Alfonso, S., Barizzone, N., Giordano, M., Chiocchetti, A., Magnani, C., Castelli, L., et al. (2005). Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum. 52, 539-547. doi: 10.1002/art.20808
10. Diekmann, U., Zarbock, R., Hendig, D., Szliska, C., Kleesiek, K., and Götting, C. (2009). Elevated circulating levels of matrix metalloproteinases MMP-2 and MMP-9 in pseudoxanthoma elasticum patients. J. Mol. Med. 87, 965-970. doi: 10.1007/s00109-009-0497-5.
11. Drumm, M. L., Konstan, M. D., Schluchter, A., Handler, R., Pace, R., Zou, F., et al. (2005). Genetic modifiers of lung disease in cystic fibrosis. N. Engl. J. Med. 34, 355-363.
12. Giacopelli, F., Marciano, R., Pistorio, A., Catarsi, P., Canini, S., Karsenty, G., et al. (2004). Polymorphisms in the osteopontin promoter affect its transcriptional activity. Physiol. Genomics 20, 87-96. doi: 10.1152/physiolgenomics.00138.2004
13. Gliem, M., Zaeytijd, J. D., Finger, R. P., Holz, F. G., Leroy, B. P., Charbel Issa, P. (2013). An update on the ocular phenotype in patients with pseudoxanthoma elasticum. Front. Genet. 4:14. doi: 10.3389/fgene.2013.00014
14. Gorgels, T. G., Hu, X., Scheffer, G. L., Van Der Wal, A. C., Toonstra, J., De Jong, P. T., et al. (2005). Disruption of Abcc6 in the mouse: novel insight in the pathogenesis of pseudoxanthoma elasticum. Hum. Mol. Genet. 14, 1763-1773. doi: 10.1093/hmg/ddi183
15. Götting, C., Hendig, D., Adam, A., Schön, S., Schulz, V., Szliska, C., et al. (2005). Elevated xylosyltransferase I activities in pseudoxanthoma elasticum (PXE) patients as a marker of stimulated proteoglycan biosynthesis. J. Mol. Med. 83, 984-992.
16. Götting, C., Kuhn, J., and Kleesiek, K. (2007). Human xylosyltransferases in health and disease. Cell. Mol. Life Sci. 64, 1498-1517.
17. Haldane, J. B. (1941). The relative importance of principal and modifying genes in determining some human diseases. J. Genet. 41, 149-157. doi: 10.1007/BF02983018
18. Hendig, D., Arndt, M., Szliska, C., Kleesiek, K., and Götting, C. (2007). SPP1 promoter polymorphisms: identification of the first modifier gene for pseudoxanthoma elasticum. Clin. Chem. 53, 829-836.
19. Hendig, D., Schulz, V., Arndt, M., Szliska, C., Kleesiek, K., and Götting, C. (2006). Role of serum fetuin-A, a major inhibitor of systemic calcification, in pseudoxanthoma elasticum. Clin. Chem. 52, 227-234.
20. Hendig, D., Zarbock, R., Szliska, C., Kleesiek, K., and Götting, C. (2008). The local calcification inhibitor matrix Gla protein in pseudoxanthoma elasticum. Clin. Biochem. 41, 407-412. doi: 10.1016/j.clinbiochem.2007.12.023
21. Hijiya, N., Setoguchi, M., Matsuura, K., Higuchi, Y., Akizuki, S., and Yamamoto, S. (1994). Cloning and characterization of the human osteopontin gene and its promoter. Biochem. J. 303(Pt 1), 255-262.
22. Hornstrup, L. S., Tybjaerg-Hansen, A., Haase, C. L., Nordestgaard, B. G., Sillesen, H., Grande, P., et al. (2011). Heterozygosity for R1141X in ABCC6 and risk of ischemic vascular disease. Circ. Cardiovasc. Genet. 4, 534-541. doi: 10.1161/CIRCGENETICS.110.958801
23. Hummelshoj, T., Ryder, L. P., Madsen, H. O., Odum, N., and Svejgaard, A. (2006). A functional polymorphism in the Eta-1 promoter is associated with allele specific binding to the transcription factor Sp1 and elevated gene expression. Mol. Immunol. 43, 980-986. doi: 10.1016/j.molimm.2005.05.012
24. Jahnen-Dechent, W., Schäfer, C., Heiss, A., and Grötzinger, J. (2001). Systemic inhibition of spontaneous calcification by the serum protein alpha 2-HS glycoprotein/fetuin. Z. Kardiol. 90(Suppl. 3), 47-56.
25. Klement, J. F., Matsuzaki, Y., Jiang, Q. J., Terlizzi, J., Choi, H. Y., Fujimoto, N., et al. (2005). Targeted ablation of the abcc6 gene results in ectopic mineralization of connective tissues. Mol. Cell Biol. 25, 8299-8310. doi: 10.1128/MCB.25.18.8299-8310.2005
26. Köblös, G., Andrikovics, H., Prohaszka, Z., Tordai, A., Varadi, A., and Aranyi, T. (2010). The R1141X loss-of-function mutation of the ABCC6 gene is a strong genetic risk factor for coronary artery disease. Genet. Test. Mol. Biomarkers 14, 75-78. doi: 10.1089/gtmb.2009.0094
27. Kool, M., Van Der Linden, M., De Haas, M., Baas, F., and Borst, P. (1999). Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. Cancer Res. 59, 175-182.
28. Korff, S., Schoensiegel, F., Riechert, N., Weichenhan, D., Katus, H. A., and Ivandic, B. T. (2006). Fine mapping of Dyscalc1, the major genetic determinant of dystrophic cardiac calcification in mice. Physiol. Genomics 25, 387-392. doi: 10.1152/physiolgenomics.00010.2006
29. Kornet, L., Bergen, A. A., Hoeks, A. P., Cleutjens, J. P., Oostra, R. J., Daemen, M. J., et al. (2004). In patients with pseudoxanthoma elasticum a thicker and more elastic carotid artery is associated with elastin fragmentation and proteoglycans accumulation. Ultrasound Med. Biol. 30, 1041-1048. doi: 10.1016/j.ultrasmedbio.2004.06.004
30. Le Boulanger, G., Labrèze, C., Croué, A., Schurgers, L. J., Chassaing, N., Wittkampf, T., et al. (2010). An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy. Am. J. Med. Genet. A 152A, 118-23. doi: 10.1002/ajmg.a.33162.
31. Le Corvaisier-Pieto, C., Joly, P., Thomine, E., Lair, G., and Lauret, P. (1996). [Generalized pseudoxanthoma elasticum combined with vitamin K dependent clotting factors deficiency]. Ann. Dermatol. Venereol. 123, 555-558.
32. Lefthériotis, G., Omarjee, L., Le Saux, O., Henrion, D., Abraham, P., Prunier, F., et al. (2013). The vascular phenotype in pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification. Front. Genet. 4:4. doi: 10.3389/fgene.2013.00004.
33. Le Saux, O., Urban, Z., Tschuch, C., Csiszar, K., Bacchelli, B., Quaglino, D., et al. (2000). Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat. Genet. 25, 223-227. doi: 10.1038/76102
34. Li, Q., Grange, D. K., Armstrong, N. L., Whelan, A. J., Hurley, M. Y., Rishavy, M. A., et al. (2009a). Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes. J. Invest. Dermatol. 129, 553-563. doi: 10.1038/jid.2008.271
35. Li, Q., Schurgers, L. J., Smith, A. C., Tsokos, M., Uitto, J., and Cowen, E. W. (2009b). Co-existent pseudoxanthoma elasticum and vitamin K-dependent coagulation factor deficiency: compound heterozygosity for mutations in the GGCX gene. Am. J. Pathol. 174, 534-540. doi: 10.2353/ajpath.2009.080865
36. Li, Q., and Uitto, J. (2010). The mineralization phenotype in Abcc6 (-/-) mice is affected by Ggcx gene deficiency and genetic background-a model for pseudoxanthoma elasticum. J. Mol. Med. 88, 173-181. doi: 10.1007/s00109-009-0522-8
37. Longas, M. O., Wisch, P., Lebwohl, M. G., and Fleischmajer, R. (1986). Glycosaminoglycans of skin and urine in pseudoxanthoma elasticum: evidence for chondroitin 6-sulfate alteration. Clin. Chim. Acta 155, 227-236. doi: 10.1016/0009-8981(86)90242-1
38. Maccari, F., Gheduzzi, D., and Volpi, N. (2003). Anomalous structure of urinary glycosaminoglycans in patients with pseudoxanthoma elasticum. Clin. Chem. 49, 380-388. doi: 10.1373/49.3.380
39. Martin, L., Chassaing, N., Delaite, D., Esteve, E., Maitre, F., and Le Bert, M. (2007). Histological skin changes in heterozygote carriers of mutations in ABCC6, the gene causing pseudoxanthoma elasticum. J. Eur. Acad. Dermatol. Venereol. 21, 368-373. doi: 10.1111/j.1468-3083.2006.01940.x
40. Martin, L., Maitre, F., Bonicel, P., Daudon, P., Verny, C., Bonneau, D., et al. (2008). Heterozygosity for a single mutation in the ABCC6 gene may closely mimic PXE: consequences of this phenotype overlap for the definition of PXE. Arch. Dermatol. 144, 301-306. doi: 10.1001/archderm.144.3.301
41. Miksch, S., Lumsden, A., Guenther, U. P., Foernzler, D., Christen-Zach, S., Daugherty, C., et al. (2005). Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. Hum. Mutat. 26, 235-248. doi: 10.1002/humu.20206
42. Munroe, P. B., Olgunturk, R. O., Fryns, J. P., Van Maldergem, L., Ziereisen, F., Yuksel, B., et al. (1999). Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. Nat. Genet. 21, 142-144. doi: 10.1038/5102
43. Neldner, K., and Struk, B. (2002). "Pseudoxanthoma elasticum," in Connective Tissue and Its Heritable Disorders, eds P. M. Royce and B. Steinmann. (New York: Wiley-Liss Inc.), 561-583. doi: 10.1002/0471221929.ch11
44. Nitschke, Y., Baujat, G., Botschen, U., Wittkampf, T., Du Moulin, M., Stella, J., et al. (2012). Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am. J. Hum. Genet. 90, 25-39. doi: 10.1016/j.ajhg.2011.11.020
45. Peloso, G. M., Demissie, S., Collins, D., Mirel, D. B., Gabriel, S. B., Cupples, L. A., et al. (2010). Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary heart disease. J. Lipid Res. 51, 3524-3532. doi: 10.1194/jlr.P008268
46. Pfendner, E. G., Vanakker, O. M., Terry, S. F., Vourthis, S., Mcandrew, P. E., Mcclain, M. R., et al. (2007). Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. J. Med. Genet. 44, 621-628. doi: 10.1136/jmg.2007.051094
47. Pisciotta, L., Tarugi, P., Borrini, C., Bellocchio, A., Fresa, R., Guerra, D., et al. (2010). Pseudoxanthoma elasticum and familial hypercholesterolemia: a deleterious combination of cardiovascular risk factors. Atherosclerosis 210, 173-176. doi: 10.1016/j.atherosclerosis.2009.11.028
48. Plomp, A. S., Bergen, A. A., Florijn, R. J., Terry, S. F., Toonstra, J., Van Dijk, M. R., et al. (2009). Pseudoxanthoma elasticum: wide phenotypic variation in homozygotes and no signs in heterozygotes for the c.3775delT mutation in ABCC6. Genet. Med. 11, 852-858. doi: 10.1097/GIM.0b013e3181c00a96
49. Plomp, A. S., Hu, X., De Jong, P. T., and Bergen, A. A. (2004). Does autosomal dominant pseudoxanthoma elasticum exist? Am. J. Med. Genet. A 126A, 403-412. doi: 10.1002/ajmg.a.20632
50. Quaglino, D., Sartor, L., Garbisa, S., Boraldi, F., Croce, A., Passi, A., et al. (2005). Dermal fibroblasts from pseudoxanthoma elasticum patients have raised MMP-2 degradative potential. Biochim. Biophys. Acta 1741, 42-47. doi: 10.1016/j.bbadis.2004.09.012
51. Ringpfeil, F., Lebwohl, M. G., Christiano, A. M., and Uitto, J. (2000). Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc. Natl. Acad. Sci. U.S.A. 97, 6001-6006. doi: 10.1073/pnas.100041297
52. Rutsch, F., Ruf, N., Vaingankar, S., Toliat, M. R., Suk, A., Hohne, W., et al. (2003). Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification. Nat. Genet. 34, 379-381. doi: 10.1038/ng1221
53. Schön, S., Schulz, V., Prante, C., Hendig, D., Szliska, C., Kuhn, J., et al. (2006). Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease course. J. Med. Genet. 43, 745-749.
54. Schulz, V., Hendig, D., Henjakovic, M., Szliska, C., Kleesiek, K., and Götting, C. (2006). Mutational analysis of the ABCC6 gene and the proximal ABCC6 gene promoter in German patients with pseudoxanthoma elasticum (PXE). Hum. Mutat. 27, 831.
55. Stenvinkel, P., Wang, K., Qureshi, A. R., Axelsson, J., Pecoits-Filho, R., Gao, P., et al. (2005). Low fetuin-A levels are associated with cardiovascular death: impact of variations in the gene encoding fetuin. Kidney Int. 67, 2383-2392. doi: 10.1111/j.1523-1755.2005.00345.x
56. Trip, M. D., Smulders, Y. M., Wegman, J. J., Hu, X., Boer, J. M., Ten Brink, J. B., et al. (2002). Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. Circulation 106, 773-775. doi: 10.1161/01.CIR.0000028420.27813.C0
57. Vanakker, O. M., Martin, L., Gheduzzi, D., Leroy, B. P., Loeys, B. L., Guerci, V. I., et al. (2007). Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. J. Invest. Dermatol. 127, 581-587. doi: 10.1038/sj.jid.5700610
58. Volpi, N., and Maccari, F. (2005). Composition of urinary glycosaminoglycans in a patient with pseudoxanthoma elasticum and familial mediterranean fever. Clin. Chim. Acta359, 207-209. doi: 10.1016/j.cccn.2005.04.008
59. Wang, J., Near, S., Young, K., Connelly, P. W., and Hegele, R. A. (2001). ABCC6 gene polymorphism associated with variation in plasma lipoproteins. J. Hum. Genet. 46, 699-705. doi: 10.1007/s100380170003
60. Wegman, J. J., Hu, X., Tan, H., Bergen, A. A., Trip, M. D., Kastelein, J. J., et al. (2005). Patients with premature coronary artery disease who carry the ABCC6 R1141X mutation have no pseudoxanthoma elasticum phenotype. Int. J. Cardiol. 100, 389-393. doi: 10.1016/j.ijcard.2004.07.012
61. Zarbock, R., Hendig, D., Szliska, C., Kleesiek, K., and Götting, C. (2007). Pseudoxanthoma elasticum: genetic variations in antioxidant genes are risk factors for early disease onset. Clin. Chem. 53, 1734-1740.
62. Zarbock, R., Hendig, D., Szliska, C., Kleesiek, K., and Götting, C. (2009). Vascular endothelial growth factor gene polymorphisms as prognostic markers for ocular manifestations in pseudoxanthoma elasticum. Hum. Mol. Genet. 18, 3344-3351. doi: 10.1093/hmg/ddp259.
63. Zarbock, R., Hendig, D., Szliska, C., Kleesiek, K., and Götting, C. (2010). Analysis of MMP2 promoter polymorphisms in patients with pseudoxanthoma elasticum. Clin. Chim. Acta 411, 1487-1490. doi: 10.1016/j.cca.2010.06.006.