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. 1997 Jan 1;25(1):147–150. doi: 10.1093/nar/25.1.147

Marfan Database (second edition): software and database for the analysis of mutations in the human FBN1 gene.

G Collod-Béroud 1, C Béroud 1, L Adès 1, C Black 1, M Boxer 1, D J Brock 1, M Godfrey 1, C Hayward 1, L Karttunen 1, D Milewicz 1, L Peltonen 1, R I Richards 1, M Wang 1, C Junien 1, C Boileau 1
PMCID: PMC146361  PMID: 9016526

Abstract

Fibrillin is the major component of extracellular microfibrils. Mutations in the fibrillin gene on chromosome 15 (FBN1) were described at first in the heritable connective tissue disorder, Marfan syndrome (MFS). More recently, FBN1 has also been shown to harbor mutations related to a spectrum of conditions phenotypically related to MFS. These mutations are private, essentially missense, generally non-recurrent and widely distributed throughout the gene. To date no clear genotype/phenotype relationship has been observed excepted for the localization of neonatal mutations in a cluster between exons 24 and 32. The second version of the computerized Marfan database contains 89 entries. The software has been modified to accomodate new functions and routines.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adès L. C., Haan E. A., Colley A. F., Richard R. I. Characterisation of four novel fibrillin-1 (FBN1) mutations in Marfan syndrome. J Med Genet. 1996 Aug;33(8):665–671. doi: 10.1136/jmg.33.8.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beaudet A. L., Tsui L. C. A suggested nomenclature for designating mutations. Hum Mutat. 1993;2(4):245–248. doi: 10.1002/humu.1380020402. [DOI] [PubMed] [Google Scholar]
  3. Beighton P., de Paepe A., Danks D., Finidori G., Gedde-Dahl T., Goodman R., Hall J. G., Hollister D. W., Horton W., McKusick V. A. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. 1988 Mar;29(3):581–594. doi: 10.1002/ajmg.1320290316. [DOI] [PubMed] [Google Scholar]
  4. Collod G., Béroud C., Soussi T., Junien C., Boileau C. Software and database for the analysis of mutations in the human FBN1 gene. Nucleic Acids Res. 1996 Jan 1;24(1):137–140. doi: 10.1093/nar/24.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Corson G. M., Chalberg S. C., Dietz H. C., Charbonneau N. L., Sakai L. Y. Fibrillin binds calcium and is coded by cDNAs that reveal a multidomain structure and alternatively spliced exons at the 5' end. Genomics. 1993 Aug;17(2):476–484. doi: 10.1006/geno.1993.1350. [DOI] [PubMed] [Google Scholar]
  6. De Paepe A., Devereux R. B., Dietz H. C., Hennekam R. C., Pyeritz R. E. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996 Apr 24;62(4):417–426. doi: 10.1002/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  7. Dietz H. C., Cutting G. R., Pyeritz R. E., Maslen C. L., Sakai L. Y., Corson G. M., Puffenberger E. G., Hamosh A., Nanthakumar E. J., Curristin S. M. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991 Jul 25;352(6333):337–339. doi: 10.1038/352337a0. [DOI] [PubMed] [Google Scholar]
  8. Dietz H. C., McIntosh I., Sakai L. Y., Corson G. M., Chalberg S. C., Pyeritz R. E., Francomano C. A. Four novel FBN1 mutations: significance for mutant transcript level and EGF-like domain calcium binding in the pathogenesis of Marfan syndrome. Genomics. 1993 Aug;17(2):468–475. doi: 10.1006/geno.1993.1349. [DOI] [PubMed] [Google Scholar]
  9. Dietz H. C., Pyeritz R. E., Puffenberger E. G., Kendzior R. J., Jr, Corson G. M., Maslen C. L., Sakai L. Y., Francomano C. A., Cutting G. R. Marfan phenotype variability in a family segregating a missense mutation in the epidermal growth factor-like motif of the fibrillin gene. J Clin Invest. 1992 May;89(5):1674–1680. doi: 10.1172/JCI115766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dietz H. C., Saraiva J. M., Pyeritz R. E., Cutting G. R., Francomano C. A. Clustering of fibrillin (FBN1) missense mutations in Marfan syndrome patients at cysteine residues in EGF-like domains. Hum Mutat. 1992;1(5):366–374. doi: 10.1002/humu.1380010504. [DOI] [PubMed] [Google Scholar]
  11. Dietz H. C., Valle D., Francomano C. A., Kendzior R. J., Jr, Pyeritz R. E., Cutting G. R. The skipping of constitutive exons in vivo induced by nonsense mutations. Science. 1993 Jan 29;259(5095):680–683. doi: 10.1126/science.8430317. [DOI] [PubMed] [Google Scholar]
  12. Godfrey M., Vandemark N., Wang M., Velinov M., Wargowski D., Tsipouras P., Han J., Becker J., Robertson W., Droste S. Prenatal diagnosis and a donor splice site mutation in fibrillin in a family with Marfan syndrome. Am J Hum Genet. 1993 Aug;53(2):472–480. [PMC free article] [PubMed] [Google Scholar]
  13. Hayward C., Porteous M. E., Brock D. J. A novel mutation in the fibrillin gene (FBN1) in familial arachnodactyly. Mol Cell Probes. 1994 Aug;8(4):325–327. doi: 10.1006/mcpr.1994.1045. [DOI] [PubMed] [Google Scholar]
  14. Hayward C., Porteous M. E., Brock D. J. Identification of a novel nonsense mutation in the fibrillin gene (FBN1) using nonisotopic techniques. Hum Mutat. 1994;3(2):159–162. doi: 10.1002/humu.1380030212. [DOI] [PubMed] [Google Scholar]
  15. Hayward C., Rae A. L., Porteous M. E., Logie L. J., Brock D. J. Two novel mutations and a neutral polymorphism in EGF-like domains of the fibrillin gene (FBN1): SSCP screening of exons 15-21 in Marfan syndrome patients. Hum Mol Genet. 1994 Feb;3(2):373–375. doi: 10.1093/hmg/3.2.373. [DOI] [PubMed] [Google Scholar]
  16. Hewett D. R., Lynch J. R., Child A., Sykes B. C. A new missense mutation of fibrillin in a patient with Marfan syndrome. J Med Genet. 1994 Apr;31(4):338–339. doi: 10.1136/jmg.31.4.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hewett D. R., Lynch J. R., Smith R., Sykes B. C. A novel fibrillin mutation in the Marfan syndrome which could disrupt calcium binding of the epidermal growth factor-like module. Hum Mol Genet. 1993 Apr;2(4):475–477. doi: 10.1093/hmg/2.4.475. [DOI] [PubMed] [Google Scholar]
  18. Kainulainen K., Karttunen L., Puhakka L., Sakai L., Peltonen L. Mutations in the fibrillin gene responsible for dominant ectopia lentis and neonatal Marfan syndrome. Nat Genet. 1994 Jan;6(1):64–69. doi: 10.1038/ng0194-64. [DOI] [PubMed] [Google Scholar]
  19. Kainulainen K., Sakai L. Y., Child A., Pope F. M., Puhakka L., Ryhänen L., Palotie A., Kaitila I., Peltonen L. Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5917–5921. doi: 10.1073/pnas.89.13.5917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Karttunen L., Raghunath M., Lönnqvist L., Peltonen L. A compound-heterozygous Marfan patient: two defective fibrillin alleles result in a lethal phenotype. Am J Hum Genet. 1994 Dec;55(6):1083–1091. [PMC free article] [PubMed] [Google Scholar]
  21. Lönnqvist L., Child A., Kainulainen K., Davidson R., Puhakka L., Peltonen L. A novel mutation of the fibrillin gene causing ectopia lentis. Genomics. 1994 Feb;19(3):573–576. doi: 10.1006/geno.1994.1110. [DOI] [PubMed] [Google Scholar]
  22. Magenis R. E., Maslen C. L., Smith L., Allen L., Sakai L. Y. Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1. Genomics. 1991 Oct;11(2):346–351. doi: 10.1016/0888-7543(91)90142-2. [DOI] [PubMed] [Google Scholar]
  23. Maslen C. L., Corson G. M., Maddox B. K., Glanville R. W., Sakai L. Y. Partial sequence of a candidate gene for the Marfan syndrome. Nature. 1991 Jul 25;352(6333):334–337. doi: 10.1038/352334a0. [DOI] [PubMed] [Google Scholar]
  24. McInnes R. R., Byers P. H. Biochemical genetics: examples of life after cloning. Curr Opin Genet Dev. 1993 Jun;3(3):475–483. doi: 10.1016/0959-437x(93)90123-7. [DOI] [PubMed] [Google Scholar]
  25. Milewicz D. M., Duvic M. Severe neonatal Marfan syndrome resulting from a de novo 3-bp insertion into the fibrillin gene on chromosome 15. Am J Hum Genet. 1994 Mar;54(3):447–453. [PMC free article] [PubMed] [Google Scholar]
  26. Milewicz D. M., Grossfield J., Cao S. N., Kielty C., Covitz W., Jewett T. A mutation in FBN1 disrupts profibrillin processing and results in isolated skeletal features of the Marfan syndrome. J Clin Invest. 1995 May;95(5):2373–2378. doi: 10.1172/JCI117930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nijbroek G., Sood S., McIntosh I., Francomano C. A., Bull E., Pereira L., Ramirez F., Pyeritz R. E., Dietz H. C. Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons. Am J Hum Genet. 1995 Jul;57(1):8–21. [PMC free article] [PubMed] [Google Scholar]
  28. Pereira L., D'Alessio M., Ramirez F., Lynch J. R., Sykes B., Pangilinan T., Bonadio J. Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum Mol Genet. 1993 Jul;2(7):961–968. doi: 10.1093/hmg/2.7.961. [DOI] [PubMed] [Google Scholar]
  29. Piersall L. D., Dietz H. C., Hall B. D., Cadle R. G., Pyeritz R. E., Francomano C. A., McIntosh I. Substitution of a cysteine residue in a non-calcium binding, EGF-like domain of fibrillin segregates with the Marfan syndrome in a large kindred. Hum Mol Genet. 1994 Jun;3(6):1013–1014. doi: 10.1093/hmg/3.6.1013. [DOI] [PubMed] [Google Scholar]
  30. Putnam E. A., Cho M., Zinn A. B., Towbin J. A., Byers P. H., Milewicz D. M. Delineation of the Marfan phenotype associated with mutations in exons 23-32 of the FBN1 gene. Am J Med Genet. 1996 Mar 29;62(3):233–242. doi: 10.1002/(SICI)1096-8628(19960329)62:3<233::AID-AJMG7>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  31. Sakai L. Y., Keene D. R., Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986 Dec;103(6 Pt 1):2499–2509. doi: 10.1083/jcb.103.6.2499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sood S., Eldadah Z. A., Krause W. L., McIntosh I., Dietz H. C. Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome. Nat Genet. 1996 Feb;12(2):209–211. doi: 10.1038/ng0296-209. [DOI] [PubMed] [Google Scholar]
  33. Ståhl-Hallengren C., Ukkonen T., Kainulainen K., Kristofersson U., Saxne T., Tornqvist K., Peltonen L. An extra cysteine in one of the non-calcium-binding epidermal growth factor-like motifs of the FBN1 polypeptide is connected to a novel variant of Marfan syndrome. J Clin Invest. 1994 Aug;94(2):709–713. doi: 10.1172/JCI117389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tynan K., Comeau K., Pearson M., Wilgenbus P., Levitt D., Gasner C., Berg M. A., Miller D. C., Francke U. Mutation screening of complete fibrillin-1 coding sequence: report of five new mutations, including two in 8-cysteine domains. Hum Mol Genet. 1993 Nov;2(11):1813–1821. doi: 10.1093/hmg/2.11.1813. [DOI] [PubMed] [Google Scholar]
  35. Wang M., Price C., Han J., Cisler J., Imaizumi K., Van Thienen M. N., DePaepe A., Godfrey M. Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal Marfan syndrome. Hum Mol Genet. 1995 Apr;4(4):607–613. doi: 10.1093/hmg/4.4.607. [DOI] [PubMed] [Google Scholar]

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