FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Volume 326:905-909 April 2, 1992 Number 14 Next

	Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Abstract

BACKGROUND. The large glycoprotein fibrillin is a structural component of elastin-containing microfibrils found in many tissues. The Marfan syndrome has been linked to the fibrillin gene on chromosome 15, but congenital contractural arachnodactyly, which shares some of the physical features of the syndrome, has been linked to the fibrillin gene on chromosome 5. METHODS. Using specific markers for the fibrillin genes, we performed genetic linkage analysis in 28 families with the Marfan syndrome and 8 families with four phenotypically related disorders--congenital contractural arachnodactyly (3 families), ectopia lentis (2), mitral-valve prolapse syndrome (2), and annuloaortic ectasia (1). RESULTS. Genetic linkage was established between the Marfan syndrome and only the fibrillin gene on chromosome 15, with a maximum lod score of 25.6 (odds for linkage, 10(25.6):1). Ectopia lentis was also linked to the fibrillin gene on chromosome 15, whereas congenital contractural arachnodactyly was linked to the fibrillin gene on chromosome 5. There was no linkage of mitral-valve prolapse to the fibrillin gene on chromosome 5; studies of chromosome 15 were not informative. Annuloaortic ectasia was not linked to either fibrillin gene. CONCLUSIONS. The Marfan syndrome appears to be caused by mutations in a single fibrillin gene on chromosome 15. Diagnosis of the Marfan syndrome by genetic linkage and analysis is now feasible in many families.

Source Information

Department of Pediatrics, University of Connecticut Health Center, Farmington 06030.

This article has been cited by other articles:

• Brinster, D. R., Rizzo, R. J., Bolman, R. M. III (2008). Ascending Aortic Aneurysms. Card Surg Adult 3: 1223-1250 [Full Text]  
• Svensson, L. G., Blackstone, E. H., Feng, J., de Oliveira, D., Gillinov, A. M., Thamilarasan, M., Grimm, R. A., Griffin, B., Hammer, D., Williams, T., Gladish, D. H., Lytle, B. W. (2007). Are Marfan Syndrome and Marfanoid Patients Distinguishable on Long-Term Follow-Up?. Ann. Thorac. Surg. 83: 1067-1074 [Abstract] [Full Text]  
• Ganesh, A., Smith, C., Chan, W., Unger, S., Quercia, N., Godfrey, M., Kraft, S., Buncic, R., Levin, A. (2006). Immunohistochemical evaluation of conjunctival fibrillin-1 in Marfan syndrome.. Arch Ophthalmol 124: 205-209 [Abstract] [Full Text]  
• Adib, N., Davies, K., Grahame, R., Woo, P., Murray, K. J. (2005). Joint hypermobility syndrome in childhood. A not so benign multisystem disorder?. Rheumatology (Oxford) 44: 744-750 [Abstract] [Full Text]  
• Laurent, S., Boutouyrie, P., Lacolley, P. (2005). Structural and Genetic Bases of Arterial Stiffness. Hypertension 45: 1050-1055 [Abstract] [Full Text]  
• Nasuti, J. F., Zhang, P. J., Feldman, M. D., Pasha, T., Khurana, J. S., Gorman, J. H. III, Gorman, R. C., Narula, J., Narula, N. (2004). Fibrillin and other matrix proteins in mitral valve prolapse syndrome. Ann. Thorac. Surg. 77: 532-536 [Abstract] [Full Text]  
• Sachdev, N. H., Coroneo, M. T., Wakefield, D., Hennessy, M. P. (2004). Isolated Ectopia Lentis: Potential Role of Matrix Metalloproteinases in Fibrillin Degradation. Arch Ophthalmol 122: 111-114 [Full Text]  
• Anderson, C. A., Rizzo, R. J., Cohn, L. H. (2003). Ascending Aortic Aneurysms. Card Surg Adult 2: 1123-1148 [Full Text]  
• Comeglio, P, Evans, A L, Brice, G, Cooling, R J, Child, A H (2002). Identification of FBN1 gene mutations in patients with ectopia lentis and marfanoid habitus. Br. J. Ophthalmol. 86: 1359-1362 [Abstract] [Full Text]  
• Wityk, R. J., Zanferrari, C., Oppenheimer, S. (2002). Neurovascular Complications of Marfan Syndrome: A Retrospective, Hospital-Based Study. Stroke 33: 680-684 [Abstract] [Full Text]  
• Loeys, B., Nuytinck, L., Delvaux, I., De Bie, S., De Paepe, A. (2001). Genotype and Phenotype Analysis of 171 Patients Referred for Molecular Study of the Fibrillin-1 Gene FBN1 Because of Suspected Marfan Syndrome. Arch Intern Med 161: 2447-2454 [Abstract] [Full Text]  
• Robinson, P. N, Godfrey, M. (2000). The molecular genetics of Marfan syndrome and related microfibrillopathies. J. Med. Genet. 37: 9-25 [Abstract] [Full Text]  
• Jondeau, G., Boutouyrie, P., Lacolley, P., Laloux, B., Dubourg, O., Bourdarias, J.-P., Laurent, S. (1999). Central Pulse Pressure Is a Major Determinant of Ascending Aorta Dilation in Marfan Syndrome. Circulation 99: 2677-2681 [Abstract] [Full Text]  
• Detter, C., Mair, H., Klein, H.-G., Georgescu, C., Welz, A., Reichart, B. (1999). Long-term prognosis of surgically-treated aortic aneurysms and dissections in patients with and without Marfan syndrome. Eur. J. Cardiothorac. Surg. 13: 416-423 [Abstract] [Full Text]  
• Zhang, M.-C., He, L., Giro, M., Yong, S. L., Tiller, G. E., Davidson, J. M. (1999). Cutis Laxa Arising from Frameshift Mutations in Exon 30 of the Elastin Gene (ELN). J. Biol. Chem. 274: 981-986 [Abstract] [Full Text]  
• Kanwar, Y. S., Ota, K., Yang, Q., Kumar, A., Wada, J., Kashihara, N., Peterson, D. R. (1998). Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development. Am. J. Physiol. Renal Physiol. 275: F710-F723 [Abstract] [Full Text]  
• Maron, B. J., Moller, J. H., Seidman, C. E., Vincent, G. M., Dietz, H. C., Moss, A. J., Towbin, J. A., Sondheimer, H. M., Pyeritz, R. E., McGee, G., Epstein, A. E. (1998). Impact of Laboratory Molecular Diagnosis on Contemporary Diagnostic Criteria for Genetically Transmitted Cardiovascular Diseases: Hypertrophic Cardiomyopathy, Long-QT Syndrome, and Marfan Syndrome : A Statement for Healthcare Professionals From the Councils on Clinical Cardiology, Cardiovascular Disease in the Young, and Basic Science, American Heart Association. Circulation 98: 1460-1471 [Full Text]  
• Gillinov, A. M., Zehr, K. J., Redmond, J. M., Gott, V. L., Deitz, H. C., Reitz, B. A., Laschinger, J. C., Cameron, D. E. (1997). Cardiac Operations in Children With Marfan's Syndrome: Indications and Results. Ann. Thorac. Surg. 64: 1140-1144 [Abstract] [Full Text]  
• Fleischer, K. J., Nousari, H. C., Anhalt, G. J., Stone, C. D., Laschinger, J. C. (1997). Immunohistochemical Abnormalities of Fibrillin in Cardiovascular Tissues in Marfan's Syndrome. Ann. Thorac. Surg. 63: 1012-1017 [Abstract] [Full Text]  
• Lipscomb, K. J, Clayton-Smith, J., Harris, R. (1997). Evolving phenotype of Marfan's syndrome. Arch. Dis. Child. 76: 41-46 [Abstract] [Full Text]  
• DIETZ, F. R., MATHEWS, K. D. (1996). Current Concepts Review - Update on the Genetic Bases of Disorders with Orthopaedic Manifestations. JBJS 78: 1583-98 [Full Text]  
• Reinhardt, D. P., Sasaki, T., Dzamba, B. J., Keene, D. R., Chu, M.-L., Gohring, W., Timpl, R., Sakai, L. Y. (1996). Fibrillin-1 and Fibulin-2 Interact and Are Colocalized in Some Tissues. J. Biol. Chem. 271: 19489-19496 [Abstract] [Full Text]  
• van den Berg, J.S.P., Limburg, M., Hennekam, R.C.M. (1996). Is Marfan Syndrome Associated With Symptomatic Intracranial Aneurysms?. Stroke 27: 10-12 [Abstract] [Full Text]  
• Finkbohner, R., Johnston, D., Crawford, E. S., Coselli, J., Milewicz, D. M. (1995). Marfan Syndrome : Long-term Survival and Complications After Aortic Aneurysm Repair. Circulation 91: 728-733 [Abstract] [Full Text]  
• Payne, R. M., Johnson, M. C., Grant, J. W., Strauss, A. W. (1995). Toward a Molecular Understanding of Congenital Heart Disease. Circulation 91: 494-504 [Abstract] [Full Text]  
• Kielty, C., Rantamaki, T, Child, A., Shuttleworth, C., Peltonen, L (1995). Cysteine-to-arginine point mutation in a 'hybrid' eight-cysteine domain of FBN1: consequences for fibrillin aggregation and microfibril assembly. J. Cell Sci. 108: 1317-1323 [Abstract]  
• Pereira, L., Levran, O., Ramirez, F., Lynch, J. R., Sykes, B., Pyeritz, R. E., Dietz, H. C. (1994). A Molecular Approach to the Stratification of Cardiovascular Risk in Families with Marfan's Syndrome. NEJM 331: 148-153 [Abstract] [Full Text]  
• Schwartz, J., Madjar, J., Rosenfeld, V. (1994). Complicated Marfan's Syndrome with Unusual Longevity: A Case History. ANGIOLOGY 45: 663-665 [Abstract]  
• Gillinov, A. M., Hulyalkar, A., Cameron, D. E., Cho, P. W., Greene, P. S., Reitz, B. A., Pyeritz, R. E., Gott, V. L. (1994). Mitral valve operation in patients with the Marfan syndrome. J. Thorac. Cardiovasc. Surg. 107: 724-731 [Abstract] [Full Text]