Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome

Journal of Clinical Investigation

Volumn 114, Issue 2, 2004, Pages 172-181

  Judge, Daniel P ^a   Biery, Nancy J ^b   Keene, Douglas R ^c   Geubtner, Jessica ^a   Myers, Loretha ^b   Huso, David L ^d   Sakai, Lynn Y ^c   Dietz, Harry C ^b,d,e  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; CYSTEINE; FIBRILLIN 1; GLYCINE; MONOCLONAL ANTIBODY; MUTANT PROTEIN;

ANIMAL MODEL; ANIMAL TISSUE; AORTA WALL; ARTICLE; CONNECTIVE TISSUE DISEASE; CONTROLLED STUDY; DEGENERATION; DOMINANT INHERITANCE; DOMINANT NEGATIVE MUTATION; FBN1 GENE; FIBER; GENE; GENE MUTATION; GENE OVEREXPRESSION; GENETIC DISORDER; HAPLOINSUFFICIENCY; HAPLOTYPE; HETEROZYGOSITY; HOMOLOGOUS RECOMBINATION; IMMUNOHISTOCHEMISTRY; MARFAN SYNDROME; MICROFIBRIL ASSEMBLY; MICROFIBRIL DEPOSITION; MISSENSE MUTATION; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN INTERACTION; PROTEIN POLYMERIZATION; SKELETON MALFORMATION; TRANSGENIC MOUSE; TRANSGENICS; WILD TYPE; YEAST ARTIFICIAL CHROMOSOME;

ABNORMALITIES, MULTIPLE; ALLELES; ANIMALS; AORTA; CARDIOVASCULAR ABNORMALITIES; DISEASE MODELS, ANIMAL; EPITOPES; GENE DOSAGE; GENES, DOMINANT; HUMANS; MARFAN SYNDROME; MICE; MICE, TRANSGENIC; MICROFIBRILS; MICROFILAMENT PROTEINS; MUTATION; PHENOTYPE; SKIN; TRANSGENES;

EID: 4043070821     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI200420641     Document Type: Article

References (51)

1. Pyeritz, R.E. 1997. Marfan syndrome and other disorders of fibrillin. In Principles and practice of medical genetics. D.L. Rimoin, J.M. Connor, and R.E. Pyeritz, editors. Churchill Livingstone. New York, New York, USA
2. Gray, J. R., et al. 1994. Ascertainment and severity of Marfan syndrome in a Scottish population. J. Med. Genet. 31:51-54.
3. Silverman, D.I., et al. 1995. Life expectancy in the Marfan syndrome. Am. J. Cardiol. 75:157-160.
4. Dietz, H.C., et al. 1991. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 352:337-339.
5. Dietz, H.C., et al. 1995. The question of heterogeneity in Marfan syndrome. Nat. Genet. 9:228-231.
6. Kainulainen, K., et al. 1991. Marfan syndrome: no evidence for heterogeneity in different populations, and more precise mapping of the gene. Am. J. Hum. Genet. 49:662-667.
7. Sakai, L.Y., Keene, D.R., and Engvall, E. 1986. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J. Cell Biol. 103:2499-2509.
8. Godfrey, M., et al. 1990. Cosegregation of elastin-associated microfibrillar abnormalities with the Marfan phenotype in families. Am. J. Hum. Genet. 46:652-660.
9. Hollister, D.W., Godfrey, M., Sakai, L.Y., and Pyeritz, R.E. 1990. Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N. Engl. J. Med. 323:152-159.
10. Godfrey, M., et al. 1990. Unilateral microfibrillar abnormalities in a case of asymmetric Marfan syndrome. Am. J. Hum. Genet. 46:661-671.
11. Eldadah, Z.A., Brenn, T., Furthmayr, H., and Dietz, H.C. 1995. Expression of a mutant human fibrillin allele upon a normal human or murine generic background recapitulates a Marfan cellular phenotype. J. Clin. Invest. 95:874-880.
12. Kielty, C.M., Phillips, J.E., Child, A.H., Pope, F.M., and Shuttleworth, C.A. 1994. Fibrillin secretion and microfibril assembly by Marfan dermal fibroblasts. Matrix Biol. 14:191-199.
13. Brenn, T., Aoyama, T., Francke, U., and Furthmayr, H. 1996. Dermal fibroblast culture as a model system for studies of fibrillin assembly and pathogenetic mechanisms: defects in distinct groups of individuals with Marfan's syndrome. Lab. Invest. 75:389-402.
14. Collod-Beroud, G., et al. 1998. Marfan database (third edition): new mutations and new routines for the software. Nucleic Acids Res. 26:229-233.
15. Frischmeyer, P.A., and Dietz, H.C. 1999. Nonsense-mediated mRNA decay in health and disease. Hum. Mol. Genet. 8:1893-1900.
16. Hewett, D., Lynch, J., Child, A., Firth, H., and Sykes, B. 1994. Differential allelic expression of a fibrillin gene (FBN1) in patients with Marfan syndrome. Am. J. Hum. Genet. 55:447-452.
17. Dietz, H.C., et al. 1993. Four novel FBN1 mutations: significance for mutant transcript level and EGF-like domain calcium binding in the pathogenesis of Marfan syndrome. Genomics. 17:468-475.
18. Schrijver, I., et al. 2002. Premature termination mutations in FBN1: distinct effects on differential allelic expression and on protein and clinical phenotypes. Am. J. Hum. Genet. 71:223-237.
19. Hutchinson, S., et al. 2003. Allelic variation in normal human FBN1 expression in a family with Marfan syndrome: a potential modifier of phenotype? Hum. Mol. Genet. 12:2269-2276.
20. Nijbroek, G., et al. 1995. Fifteen novel FBN1 mutations causing Marfan syndrome detected by hetero-duplex analysis of genomic amplicons. Am. J. Hum. Genet. 57:8-21.
21. Pereira, L., et al. 1997. Targeting of the gene encoding fibrillin-1 recapitulates the vascular aspect of Marfan syndrome. Nat. Genet. 17:218-222.
22. Pereira, L., et al. 1999. Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1. Proc. Natl. Acad. Sci. U. S. A. 96:3819-3823.
23. Liu, W.O., Oefner, P.J., Qian, C., Odom, R.S., and Francke, U. 1997. Denaturing HPLC-identified novel FBN1 mutations, polymorphisms, and sequence variants in Marfan syndrome and related connective tissue disorders. Genet. Test. 1:237-242.
24. Schrijver, I., Liu, W., Brenn, T., Furthmayr, H., and Francke, U. 1999. Cysteine substitutions in epidermal growth factor-like domains of fibrillin-1: distinct effects on biochemical and clinical phenotypes. Am. J. Hum. Genet. 65:1007-1020.
25. Bunton, T.E., et al. 2001. Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome. Circ. Res. 88:37-43.
26. Gayraud, B., Keene, D.R., Sakai, L.Y., and Ramirez, F. 2000. New insights into the assembly of extracellular microfibrils from the analysis of the fibrillin 1 mutation in the tight skin mouse. J. Cell Biol. 150:667-680.
27. Neptune, E.R., et al. 2003. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat. Genet. 33:407-411.
28. Abraham, P.A., Perejda A.J., Carnes, W.H., and Uitto, J. 1982. Marfan syndrome. Demonstration of abnormal elastin in aorta. J. Clin. Invest. 70:1245-1252.
29. Greenlee, T.K.J., Ross, R., and Hartman, J.L. 1966. The fine structure of elastic fibers. J. Cell. Biol. 30:59-71.
30. Fahrenbach, W.H., Sandberg, L.B., and Cleary, E.G. 1966. Ultrascructural studies on early elastogenesis. Anat. Rec. 155:563-576.
31. Trask, T.M., et al. 2000. Interaction of tropoelastin with the amino-terminal domains of fibrillin-1 and Fibrillin-2 suggests a role for the fibrillins in elastic fiber assembly. J. Biol. Chem. 275:24400-24406.
32. Baldock, C., et al. 2001. The supramolecular organization of fibrillin-rich microfibrils. J. Cell Biol. 152:1045-1056.
33. Sakai, L.Y., Keene, D.R., Glanville, R.W., and Bachinger, H.P. 1991. Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. J. Biol. Chem. 266:14763-14770.
34. Trask, T.M., Ritty, T.M., Broekelmann, T., Tisdale, C., and Mecham, R.P. 1999. N-terminal domains of fibrillin 1 and fibrillin 2 direct the formation of homodimers: a possible first step in microfibril assembly. Biochem. J. 340:693-701.
35. Halliday, D., et al. 1999. Molecular analysis of eight mutations in FBN1. Hum. Genet. 105:587-597.
36. Raghunath, M., Superti-Furga, A., Godfrey, M., and Steinmann, B. 1993. Decreased extracellular deposition of fibrillin and decorin in neonatal Marfan syndrome fibroblasts. Hum. Genet. 90:511-515.
37. Tiedemann, K., Batge, B., Muller, P.K., and Reinhardt, D.P. 2001. Interactions of fibrillin-1 with heparin/heparan sulfate, implications for microfibrillar assembly. J. Biol. Chem. 276:36035-36042.
38. Handford, P., et al. 1995. The calcium binding properties and molecular organization of epidermal growth factor-like domains in human fibrillin-1. J. Biol. Chem. 270:6751-6756.
39. Guo, D., Tan, F.K., Cantu, A., Plon, S.E., and Milewicz, D.M. 2001. FBN1 exon 2 splicing error in a patient with Marfan syndrome. Am. J. Med. Genet. 101:130-134.
40. Hindson, V.J., et al. 1999. Fibrillin degradation by matrix metalloproteinases: identification of amino- and carboxy-terminal cleavage sites. FEBS Lett. 452:195-198.
41. Booms, P., Tiecke, F., Rosenberg, T., Hagemeier, C., and Robinson, P.N. 2000. Differential effect of FBN1 mutations on in vitro proteolysis of recombinant fibrillin-1 fragments. Hum. Genet. 107:216-224.
42. Reinhardt, D.P., Ono, R.N., and Sakai, L.Y. 1997. Calcium stabilizes fibrillin-1 against proteolytic degradation. J. Biol. Chem. 272:1231-1236.
43. Reinhardt, D.P., et al. 2000. Mutations in calcium-binding epidermal growth factor modules render fibrillin-1 susceptible to proteolysis. A potential disease-causing mechanism in Marfan syndrome. J. Biol. Chem. 275:12339-12345.
44. Pavan, W.J., Hieter, P., Sears, D., Burkhoff, A., and Reeves, R.H. 1991. High-efficiency yeast artificial chromosome fragmentation vectors. Gene. 106:125-127.
45. Spencer, F., et al. 1994. Yeast kar1 mutants provide an effective method for YAC transfer to new hosts. Genomics. 22:118-126.
46. Reinhardt, D.P., et al. 1996. Fibrillin-1: organization in microfibrils and structural properties. J. Mol. Biol. 258:104-116.
47. Southern, E.M. 1975, Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98:503-517.
48. Montgomery, R.A., and Dietz, H.C. 1997. Inhibition of fibrillin 1 expression using U1 snRNA as a vehicle for the presentation of antisense targeting sequence. Hum. Mol. Genet. 6:519-525.
49. Charbonneau, N.L., et al. 2003. Fibrillins can coassemble in fibrils, bur fibrillin fibril composition displays cell-specific differences. J. Biol. Chem. 278:2740-2749.
50. LoRusso, F.J., and Font, R.L. 1999. Use of agar in ophthalmic pathology: a technique to improve the handling and diagnosis of temporal artery biopsies, subfoveal membranes, lens capsules, and other ocular tissues. Ophthalmology. 106:2106-2108.
51. Sakai, L.Y., and Keene, D.R. 1994, Fibrillin: monomers and microfibrils. Methods Enzymol. 245:29-52.