Abstract
Marfan syndrome is an autosomal-dominant connective tissue disorder characterized by pleiotropic manifestations involving the skeletal, ocular, and cardiovascular systems and resulting from mutations in the gene for fibrillin, FBN1. The clinical diagnosis is based on a set of well-defined clinical criteria (Ghent nosology). Nevertheless, the age-related nature of some clinical manifestations and the variable phenotypic expression of the disorder may hamper the diagnosis. In those instances, molecular analysis of the FBN1 gene is helpful to identify at-risk individuals. Mutations are spread over the entire FBN1 gene and there are no particular hot spots. Different standard methodologies are available to identify these mutations, however, one of the most sensitive techniques is denaturing high-performance liquid chromatography. This approach allows the performance of the analysis in a semi-automated manner and has a mutation detection rate of approx 95%.
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References
Gray, J. R., Bridges, A. B., Faed, M. J, et al. (1994) Ascertainment and severity of Marfan syndrome in a Scottish population. J. Med. Genet. 31, 51–54.
Pyeritz, R. E. (2000) The Marfan syndrome. Annu. Rev. Med. 51, 481–510.
De Paepe, A., Devereux, R. B., Dietz, H. C., Hennekam, R. C., and Pyeritz, R. E.(1996) Revised diagnostic criteria for the Marfan syndrome. Am. J. Med. Genet. 62, 417–426.
Kainulainen, K., Pulkkinen, L., Savolainen, A., Kaitila, I., and Peltonen, L. (1990) Location on chromosome 15 of the gene defect causing Marfan syndrome. N. Engl.J. Med. 323, 935–939.
Lee, B., Godfrey, M., Vitale, E., et al. (1991) Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature 352, 330–334.
Dietz, H. C., Cutting, G. R., Pyeritz, R. E., et al. (1991) Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352, 337–339.
Sakai, L. Y., Keene, D. R., and Engvall, E. (1986) Fibrillin, a new 350-kD glyco-protein, is a component of extracellular microfibrils. J. Cell Biol. 103, 2499–2509.
Handford, P. A., Mayhew, M., and Brownlee, G. G. (1991) Calcium binding to fibrillin? Nature 353, 395.
Pereira, L., D’Alessio, M., Ramirez, F., et al. (1993) Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum.Mol. Genet. 2, 1762.
Collod-Beroud, G. and Boileau, C. (2002) Marfan syndrome in the third Millen-nium. Eur. J. Hum. Genet. 10, 673–681.
Gray, J. R., Bridges, A. B., Faed M. J., et al. (1994) Ascertainment and severity of Marfan syndrome in a Scottish population. J. Med. Genet. 31, 51–54.
Park, E. S., Putnam, E. A., Chitayat, D., Child, A., and Milewicz, D. M. (1998) Clustering of FBN2 mutations in patients with congenital contractural arachno-dactyly indicates an important role of the domains encoded by exons 24 through 34 during human development. Am. J. Med. Genet. 78, 350–355.
Ganguly, A., Rock, M. J., and Prockop, D. J. (1993) Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes. Proc. Natl. Acad. Sci. USA 90, 10,325–10,429.
Pepe, G., Giusti, B., Evangelisti, L., et al. (2001) Fibrillin-1 (FBN1) gene frame-shift mutations in Marfan patients: genotype-phenotype correlation. Clin. Genet. 59, 444–450.
Tynan, K., Comeau, K., Pearson, M., et al. (1993) Mutation screening of complete fibrillin-1 coding sequence: report of five new mutations, including two in 8-cys-teine domains. Hum. Mol. Genet. 2, 1813–1821.
Comeglio, P., Evans, A. L., Brice, G. W., and Child, A. H. (2001) Detection of six novel FBN1 mutations in British patients affected by Marfan syndrome. Hum. Mutat. 18, 251.
Xiao, W. and Oefner, P. J. (2001) Denaturing high-performance liquid chromatog-raphy:a review. Hum. Mutat. 17, 439–474.
Liu, W. O., Oefner, P. J., Qian, C., Odom, R. S., and Francke, U. (1997) Denatur-ing HPLC-identified novel FBN1 mutations, polymorphisms, and sequence vari-ants in Marfan syndrome and related connective tissue disorders. Genet. Test. 1, 237–242.
Frueh, F. W. and Noyer-Weidner, M. (2003) The use of denaturing high-perfor-mance liquid chromatography (DHPLC) for the analysis of genetic variations: impact for diagnostics and pharmacogenetics. Clin. Chem. Lab. Med. 41, 452–461.
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Coucke, P., Van Acker, P., De Paepe, A. (2006). Mutation Analysis of the FBN1 Gene in Patients With Marfan Syndrome. In: Kearns-Jonker, M. (eds) Congenital Heart Disease. Methods in Molecular Medicine, vol 126. Humana Press. https://doi.org/10.1385/1-59745-088-X:81
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DOI: https://doi.org/10.1385/1-59745-088-X:81
Publisher Name: Humana Press
Print ISBN: 978-1-58829-375-6
Online ISBN: 978-1-59745-088-1
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