Marfan syndrome
The Marfan syndrome is common autosomal dominant heritable disorder of connective tissue with prominent manifestations in the cardiovascular system, the skeleton, and the eye. Mutations in the gene for fibrillin-1 (FBN1) are responsible for the Marfan syndrome. Fibrillin-1 is the main component of a class of extracellular microfibrils that are found together with elastin as elastic fibers in tissues such as the aorta as well as isolated in tissues such as the ciliary zonule. The pathogenesis of the Marfan syndrome is still not well understood at the molecular level. A combination of defects is likely to occur as a result of FBN1 mutations, including dominant negative effects on the aggregation of the highly polymeric microfibrils, reduced tissue homeostasis, and increased susceptibility of fibrillin to proteolysis.
Our lab has been interested primarily in FBN1 mutation analysis, in genotype-phenotype correlations, and in the investigation of the effects of FBN1 mutations with the use of recombinant fibrillin-1 fragments, especially with regard to the ability of fibrillin-1 fragments to induce secondary biological effects such as MMP upregulation or to induce monocyte/macrophage chemotaxis.Journal articles
- Guo G, Bauer S, Hecht J, Schulz MH, Busche A, Robinson PN (2008) A short ultraconserved sequence drives transcription from an alternate FBN1-promoter. Int J Biochem Cell Biol. 40:638-650.
- Guo G, Booms P, Halushka M, Dietz HC, Ney A, Stricker S, Hecht J, Mundlos S, Robinson PN* (2006) Induction of macrophage chemotaxis by aortic extracts of the mgR Marfan mouse model and a GxxPG-containing fibrillin-1 fragment. Circulation. 114:1855-62.
- Robinson PN*, Arteaga-Solis E, Baldock C, Collod-Beroud G, Booms P, De Paepe A, Dietz HC, Guo G, Handford PA, Judge DP, Kielty CM, Loeys B, Milewicz DM, Ney A, Ramirez F, Reinhardt DP, Tiedemann K, Whiteman P, Godfrey M. (2006) The molecular genetics of Marfan syndrome and related disorders. J Med Genet 43:769-87.
- Booms P, Ney A, Barthel F, Moroy G, Counsell D, Gille C, Guo G, Pregla R, Mundlos S, Alix AJ, Robinson PN* (2006) A fibrillin-1-fragment containing the elastin-binding-protein GxxPG consensus sequence upregulates matrix metalloproteinase-1: biochemical and computational analysis. J Mol Cell Cardiol 40:234-46.
- Ney A, Booms P, Epple G, Morgelin M, Guo G, Kettelgerdes G, Gessner R, Robinson PN* (2006) Calcium-dependent self-association of the C-type lectin domain of versican. Int J Biochem Cell Biol 38:23-9.
- Robinson PN*, Neumann LM, Demuth S, Enders H, Jung U, Konig R, Mitulla B, Muller D, Muschke P, Pfeiffer L, Prager B, Somer M, Tinschert S. (2005) Shprintzen-Goldberg syndrome: fourteen new patients and a clinical analysis Am J Med Genet A. 135:251-62.
- Booms P, Pregla R, Ney A, Barthel F, Reinhardt DP, Pletschacher A, Mundlos S, Robinson PN* (2005) RGD-containing fibrillin-1 fragments upregulate matrix metalloproteinase expression in cell culture: a potential factor in the pathogenesis of the Marfan syndrome. Hum Genet 116:51-61.
- Katzke S, Booms P, Tiecke F, Palz M, Pletschacher A, Turkmen S, Neumann LM, Pregla R, Leitner C, Schramm C, Lorenz P, Hagemeier C, Fuchs J, Skovby F, Rosenberg T, Robinson PN* (2002) TGGE screening of the entire FBN1 coding sequence in 126 individuals with marfan syndrome and related fibrillinopathies Hum Mutat 20:197-208
- Robinson PN*, Booms P, Katzke S, Ladewig M, Neumann L, Palz M, Pregla R, Tiecke F, Rosenberg T (2002) Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies Hum Mutat 20:153-61
- Robinson PN*, Booms P (2001) The molecular pathogenesis of the Marfan syndrome Cell Mol Life Sci. 58:1698-707
- Tiecke F, Katzke S, Booms P, Robinson PN*, Neumann L, Godfrey M, Mathews KR, Scheuner M, Hinkel GK, Brenner RE, Hovels-Gurich HH, Hagemeier C, Fuchs J, Skovby F, Rosenberg T (2001) Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40 Eur J Hum Genet 9:13-21
- Booms P, Tiecke F, Rosenberg T, Hagemeier C,Robinson PN* (2000) Differential effect of FBN1 mutations on in vitro proteolysis of recombinant fibrillin-1 fragments Hum Genet 107:216-24
- Palz M, Tiecke F, Booms P, Goldner B, Rosenberg T, Fuchs J, Skovby F, Schumacher H, Kaufmann UC, von Kodolitsch Y, Nienaber CA, Leitner C, Katzke S, Vetter B, Hagemeier C, Robinson PN* (2000) Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation Am J Med Genet 91:212-21
- Robinson PN*, Godfrey M (2000) The molecular genetics of Marfan syndrome and related microfibrillopathies J Med Genet. 37:9-25
- Booms P, Cisler J, Mathews KR, Godfrey M, Tiecke F, Kaufmann UC, Vetter U, Hagemeier C, Robinson PN* (1999) Novel exon skipping mutation in the fibrillin-1 gene: two 'hot spots' for the neonatal Marfan syndrome Clin Genet 55:110-7
- Booms P, Withers AP, Boxer M, Kaufmann UC, Hagemeier C, Vetter U, Robinson PN* (1997) A novel de novo mutation in exon 14 of the fibrillin-1 gene associated with delayed secretion of fibrillin in a patient with a mild Marfan phenotype Hum Genet. 100:195-200
The Marfan Syndrome: A Primer for Clinicians and Scientists
This book provides a comprehensive overview of the salient clinical aspects of Marfan syndrome and related disorders. Mutations in FBN1 and the role of FBN1 mutation analysis in diagnosis are discussed. Fibrillin and microfibril physiology and pathophysiology are reviewed.
The book is jointly published by Landes Bioscience and Kluwer Academic Publishers and individual chapters are available online at Eurekah.com. It was edited jointly by Peter N. Robinson and Maurice Godfrey.
100% of the profits of the editors have been donated to the German Marfan Patient organization MarfanHilfe (Deutschland) e.V. and the American National Marfan Foundation.
Book Chapters
- Peter N. Robinson, Marfan Syndrome. Chapter in the Nature Encyclopedia of the Human Genome, David N. Cooper (editor-in-chief), Nature Publishing Group, London, 2003.
- An online version of the above article is available in the Encyclopedia of Life Sciences.
- P.N. Robinson. Molecular Diagnosis of the Marfan Syndrome. In. P.A. Doevendans and A.A.M. Wilde, Cardiovascular Genetics for Clinicians. Kluwer Academic Publishers, 2001
- Hartmut Peters and Peter N. Robinson. Temperature and Denaturing Gradient Gel Electrophoresis. In G.P. Patrinos and W. Ansorge, Molecular Diagnostics, Elsevier Academic Press, 2005.
- Peter N. Robinson, Yskert von Kodolitsch. Marfan Syndrome. In Current Pediatric Therapy , 18th edition, 2006.
- Several chapters in the German-language Guide for Patients, „Marfan-Syndrom - Ein Ratgeber für Patienten, Angehörige und Betreuende“ Steinkoppf-Verlag, 2006.