Pseudoxanthoma elasticum: Clinical phenotypes, molecular genetics and putative pathomechanisms

Experimental Dermatology

Volumn 18, Issue 1, 2009, Pages 1-11

  Li, Qiaoli ^a   Jiang, Qiujie ^a   Pfendner, Ellen ^b   Váradi, András ^c   Uitto, Jouni ^a  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b GENEDX   (United States)

^c INSTITUTE OF ENZYMOLOGY   (Hungary)

Author keywords

ABC transporters; Heritable skin diseases; Pathologic connective tissue mineralisation

Indexed keywords

ABC TRANSPORTER; ABC TRANSPORTER C6; ELASTIN; FIBRILLIN 1; FIBRILLIN 2; MATRIX GLA PROTEIN; MATRIX PROTEIN; MULTIDRUG RESISTANCE PROTEIN 6; PROTEIN LYSINE 6 OXIDASE; UNCLASSIFIED DRUG; VITAMIN K DEPENDENT CARBOXYLASE;

BLOOD CLOTTING DISORDER; CHROMOSOME 15; CHROMOSOME 5; CHROMOSOME 7Q; CUTIS LAXA; GENE DELETION; GENE INTERACTION; HETEROZYGOSITY; HISTOPATHOLOGY; HUMAN; MINERALIZATION; MISSENSE MUTATION; MOLECULAR GENETICS; MUTATIONAL ANALYSIS; NONHUMAN; NONSENSE MUTATION; PHENOTYPE; PROTEIN FUNCTION; PSEUDOXANTHOMA ELASTICUM; REVIEW; SEQUENCE HOMOLOGY; SKIN DEFECT;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; BIOLOGICAL TRANSPORT; BIOPSY; HETEROZYGOTE; HUMANS; KIDNEY; LIVER; MICE; MICE, KNOCKOUT; MODELS, GENETIC; MOLECULAR BIOLOGY; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; MUTATION; PSEUDOXANTHOMA ELASTICUM;

EID: 57649232758     PISSN: 09066705     EISSN: 16000625     Source Type: Journal    
DOI: 10.1111/j.1600-0625.2008.00795.x     Document Type: Review

References (66)

1. Neldner K H, Struk B. Pseudoxanthoma elasticum. In: Royce P M, Steinmann B, eds. Connective Tissue and its Heritable Disorders: Molecular, Genetic and Medical Aspects. New York: Wiley-Liss, Inc., 2002: 561-583.
2. McKusick V A Heritable disorders of connective tissues, 4th edn. Mosby, St. Louis, 1972, pp. 475-520.
3. Uitto J, Ringpfeil F. Heritable diseases affecting the elastic fibers: cutis laxa, pseudoxanthoma elasticum and related disorders. In: Rimoin D L, Connor J M, Pyeritz R E, Korf B R, eds. Principles and Practice of Genetics, 5th edn. Philadelphia: Churchill Livingstone, 2007: 3647-3670.
4. Chassaing N, Martin L, Calvas P, Le Bert M, Hovnanian A. Pseudoxanthoma elasticum: A clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. J Med Genet 2005: 42: 881-892.
5. Ringpfeil F, McGuigan K, Fuchsel L et al. Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity. J Invest Dermatol 2006: 126: 782-786.
6. Martin L, Chassaing N, Delaite D, Esteve E, Maitre F, Le Bert M. Histological skin changes in heterozygote carriers of mutations in ABCC6, the gene causing pseudoxanthoma elasticum. J Eur Acad Dermatol Venereol 2007: 21: 368-373.
7. Martin L, Maître F, Bonicel P et al. 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 2008: 144: 301-306.
8. Trip M D, Smulders Y M, Wegman J J et al. Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. Circulation 2002: 106: 773-775.
9. Christiano A M, Lebwohl M G, Boyd C D, Uitto J. Workshop on pseudoxanthoma elasticum: Molecular biology and pathology of the elastic fibers. Jefferson Medical College, Philadelphia, Pennsylvania. J Invest Dermatol 1992: 99: 660-663.
10. Raybould M C, Birley A J, Moss C, Hultén M, McKeown C M. Exclusion of an elastin gene (ELN) mutation as the cause of pseudoxanthoma elasticum (PXE) in one family. Clin Genet 1994: 45: 48-51.
11. Le Saux O, Urban Z, Göring H H et al. Pseudoxanthoma elasticum maps to an 820-kb region of the p13.1 region of chromosome 16. Genomics 1999: 62: 1-10.
12. Cai L, Struk B, Adams M D et al. A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: High-resolution mapping and genomic structure. J Mol Med 2000: 78: 36-46.
13. Ringpfeil F, Lebwohl M G, Christiano A M, Uitto J. Pseudoxanthoma elasticum: Mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci USA 2000: 97: 6001-6006.
14. Le Saux O, Urban Z, Tschuch C et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet 2000: 25: 223-227.
15. Bergen A A, Plomp A S, Schuurman E J et al. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet 2000: 25: 228-231.
16. Struk B, Cai L, Zäch S et al. Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum. J Mol Med 2000: 78: 282-286.
17. Belinsky M G, Kruh G D. MOAT-E (ARA) is a full length MRP/cMOAT subfamily transporter expressed in kidney and liver. Br J Cancer 1999: 80: 1342-1349.
18. Scheffer G L, Hu X, Pijnenborg A C, Wijnholds J, Bergen A A, Scheper R J. MRP6 (ABCC6) detection in normal human tissues and tumors. Lab Invest 2002: 82: 515-518.
19. Ringpfeil F, Pulkkinen L, Uitto J. Molecular genetics of pseudoxanthoma elasticum. Exp Dermatol 2001: 10: 221-228.
20. Pulkkinen L, Nakano A, Ringpfeil F, Uitto J. Identification of ABCC6 pseudogenes on human chromosome 16p: Implications for mutation detection in pseudoxanthoma elasticum. Hum Genet 2001: 109: 356-365.
21. Pfendner E G, Vanakker O, Terry S F et al. Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. J Med Genet 2007: 44: 621-628.
22. Iliás A, Urban Z, Seidl T L et al. Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem 2002: 277: 16860-16867.
23. Belinsky M G, Chen Z S, Shchaveleva I, Zeng H, Kruh G D. Characterization of the drug resistance and transport properties of multi-drug resistance protein 6 (MRP6, ABCC6). Cancer Res 2002: 62: 6172-6177.
24. Klement J F, Matsuzaki Y, Jiang Q-J et al. Targeted ablation of the ABCC6 gene results in ectopic mineralization of connective tissues. Mol Cell Biol 2005: 25: 8299-8310.
25. Gorgels T G, Hu X, Scheffer G L et al. Disruption of Abcc6 in the mouse: Novel insight in the pathogenesis of pseudoxanthoma elasticum. Hum Mol Genet 2005: 14: 1763-1773.
26. Pfendner E, Uitto J, Gerard G F, Terry S F. Pseudoxanthoma elasticum: genetic diagnostic markers. Expert Opin Med Diagn 2008: 2: 1-17.
27. Dawson R J, Locher K P. Structure of a bacterial multidrug ABC transporter. Nature 2006: 443: 180-185.
28. Dawson R J, Locher K P. Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. FEBS Lett 2007: 581:935-938.
29. Ward A, Reyes C L, Yu J, Roth C B, Chang G. Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc Natl Acad Sci USA 2007:104:19005-19010.
30. DeGorter M K, Conseil G, Deeley R G, Campbell R L, Cole S P. Molecular modeling of the human multidrug resistance protein 1 (MRP1/ABCC1). Biochem Biophys Res Commun 2008: 365: 29-34.
31. O'Mara M L, Tieleman D P. P-glycoprotein models of the apo and ATP-bound states based on homology with Sav1866 and MalK. FEBS Lett 2007: 581: 4217-4222.
32. Uitto J, Pulkkinen L, Ringpfeil F. Molecular genetics of pseudoxanthoma elasticum: A metabolic disorder at the environment-genome interface? Trends Mol Med 2001: 7: 13-17.
33. Jiang Q, Uitto J. Pseudoxanthoma elasticum: A metabolic disease? J Invest Dermatol 2006: 126: 1440-1441.
34. Jiang Q, Li Q, Uitto J. Aberrant mineralization of connective tissues in a mouse model of pseudoxanthoma elasticum: Systemic and local regulatory factors. J Invest Dermatol 2007: 127: 1392-4102.
35. Le Saux O, Bunda S, VanWart C M et al. Serum factors from pseudoxanthoma elasticum patients alter elastic fiber formation in vitro. J Invest Dermatol 2006: 126: 1497-1505.
36. Jiang Q, Endo M, Dibra F, Wang K, Uitto J Pseudoxanthoma elasticum is a metabolic disease. J Invest Dermatol 2008: PMID 18688022.
37. Capla J M, Ceradini D J, Tepper O M et al. Skin graft vascularization involves precisely regulated regression and replacement of endothelial cells through both angiogenesis and vasculogenesis. Plast Reconstr Surg 2006: 117: 836-844.
38. Passi A, Albertini R, Baccarani Contri M et al. Proteoglycan alterations in skin fibroblast cultures from patients affected with pseudoxanthoma elasticum. Cell Biochem Funct 1996: 14: 111-120.
39. Quaglino D, Boraldi F, Barbieri D, Croce A, Tiozzo R, Pasquali-Ronchetti I. Abnormal phenotype of in vitro dermal fibroblasts from patients with pseudoxanthoma elasticum (PXE). Biochim Biophys Acta 2000: 1501: 51-62.
40. Quaglino D, Sartor L, Gabrisa S et al. Dermal fibroblasts from pseudoxanthoma elasticum patients have raised MMP-2 degradative potential. Biochim Biophys Acta 2005: 1741: 42-47.
41. Sakuraoka K, Tajima S, Nishikawa T, Seyama Y. Biochemical analyses of macromolecular matrix components in patients with pseudoxanthoma elasticum. J Dermatol 1994: 21: 98-101.
42. Lebwohl M, Schwartz E, Lemlich G, Lovelace O, Shaikh-Bahai F, Fleischmajer R. Abnormalities of connective tissue components in lesional and non-lesional tissue of patients with pseudoxanthoma elasticum. Arch Dermatol Res 1993: 285: 121-126.
43. Neldner K H. Pseudoxanthoma elasticum. Clin Dermatol 1988: 6: 1-159.
44. Baccarani-Contri M, Bacchelli B, Boraldi F et al. Characterization of pseudoxanthoma elasticum-like lesions in the skin of patients with beta-thalassemia. J Am Acad Dermatol 2001: 44: 33-39.
45. Hamlin N, Beck K, Bacchelli B, Cianciulli P, Pasquali-Ronchetti I, Le Saux O. Acquired pseudoxanthoma elasticum-like syndrome in beta-thalassaemia patients. Br J Haematol 2003: 122: 852-854.
46. Pasquali-Ronchetti I, Garcia-Fernandez M I, Boraldi F et al. Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations. J Pathol 2006: 208: 54-61.
47. Zarbock R, Hendig D, Szliska C, Kleesiek K, Götting C. Pseudoxanthoma elasticum: Genetic variations in antioxidant genes are risk factors for early disease onset. Clin Chem 2007: 53: 1734-1740.
48. -/-). J Invest Dermatol 2008: 128: 1160-1164.
49. Mueller C F, Widder J D, McNally J S, McCann L, Jones D P, Harrison D G. The role of the multidrug resistance protein-1 in modulation of endothelial cell oxidative stress. Circ Res 2005: 97: 637-644.
50. Cole S P, Deeley R G. Transport of glutathione and glutathione conjugates by MRP1. Trends Pharmacol Sci 2006: 27: 438-446.
51. Shearer M J. Role of vitamin K and Gla proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care 2000: 3: 433-438.
52. Hendig D, Arndt M, Szliska C, Kleesiek K, Götting C. SPP1 promoter polymorphisms: Identification of the first modifier gene for pseudoxanthoma elasticum. Clin Chem 2007: 53: 829-836.
53. Renie W A, Pyeritz R E, Combs J, Fine S L. Pseudoxanthoma elasticum: high calcium intake in early life correlates with severity. Am J Med Genet 1984: 19: 235-244.
54. Sherer D W, Singer G, Uribarri J et al. Oral phosphate binders in the treatment of pseudoxanthoma elasticum. J Am Acad Dermatol 2005: 53: 610-615.
55. -/- mice: Effects of dietary modifications and a phosphate binder - a preliminary study. Exp Dermatol 2008: 17: 203-207.
56. Le Corvaisier-Pieto C, Joly P, Thomine E, Lair G, Lauret P. Generalized pseudoxanthoma elasticum combined with vitamin K dependent clotting factors deficiency. Ann Dermatol Venereol 1996: 123: 555-558.
57. Rongioletti F, Bertamino R, Rebora A. Generalized pseudoxanthoma elasticum with deficiency of vitamin K-dependent clotting factors. J Am Acad Dermatol 1989: 21: 1150-1152.
58. Vanakker O M, Martin L, Gheduzzi D et al. Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. J Invest Dermatol 2007: 127: 581-587.
59. Li Q, Grange D K, Armstrong N L et al. Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes. J Invest Dermatol 2008: In press.
60. Gheduzzi D, Boraldi F, Annovi G et al. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest 2007:87: 998-1008.
61. -/-). Biochem Biophys Res Commun 2007: 364: 208-213.
62. Berkner K L. The vitamin K-dependent carboxylase. Ann Rev Nutr 2005: 25: 127-149.
63. Borst P, van de Wetering K, Schlingemann R. Does the absence of ABCC6 (multidrug resistance protein 6) in patients with pseudoxanthoma elasticum prevent the liver from providing sufficient vitamin K to the periphery? Cell Cycle 2008: 7: 1575-1579.
64. Chang M, Shi M, Forman H J. Exogenous glutathione protects endothelial cells from menadione toxicity. Am J Physiol 1992: 262: L637-L643.
65. Lim J I, Bressler N M, Marsh M J, Bressler S B. Laser treatment of choroidal neovascularization in patients with angioid streaks. Am J Ophthalmol 1993: 116: 414-423.
66. Roth D B, Estafanous M, Lewis H. Macular translocation for subfoveal choroidal neovascularization in angioid streaks. Am J Ophthalmol 2001: 131: 390-392.