Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene (original) (raw)

• Letter
• Published: 25 July 1991
• Carry R. Cutting2,3,
• Reed E. Pyeritz2,3,
• Cheryl L. Maslen5,
• Lynn Y Sakai5,6,
• Glen M Corson5,
• Erik G. Puffenberger3,
• Ada Hamosh2,
• Elizabeth J. Nanthakumar2,
• Sheila M. Curristin2,
• Gail Stetten2,4,
• Deborah A. Meyers3 &
• …
• Clair A. Francomano2,3

Nature volume 352, pages 337–339 (1991)Cite this article

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Abstract

MARFAN syndrome is an inherited disorder of connective tissue manifested in the ocular, skeletal and cardiovascular systems. It is inherited as an autosomal dominant with high penetrance, but has great clinical variability1. Linkage studies have mapped the Marfan locus to chromosome 15q 15–21.3 (refs 2, 3). There have been no reports of genetic heterogeneity in the syndrome. Following the identification of fibrillin (a glycoprotein component of the extracellular microfibril4), immunohistopathological quantification of the protein in skin and fibroblast culture5, and examination of fibrillin synthesis, extracellular transport, and incorporation into the extracellular matrix (D. M. Milewicz, R.E.P., E. S. Crawford and P. H. Byers, manuscript in preparation) have demonstrated abnormalities of fibrillin metabolism in most patients. A portion of the complementary DNA encoding fibrillin has been cloned6 and mapped by in situ hybridization to chromosome 15 (ref. 7). Here we report that the fibrillin gene is linked to the Marfan phenotype (θ =0.00; logarithm of the odds (lod) = 3.9) and describe a de novo missense mutation in the fibrillin gene in two patients with sporadic disease. We thus implicate fibrillin as the protein defective in patients with the Marfan syndrome.

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Authors and Affiliations

1. Division of Pediatric Cardiology, Department of Pediatrics The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
   Harry C. Dietz
2. Center for Medical Genetics, Departments of Pediatrics The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
   Carry R. Cutting, Reed E. Pyeritz, Ada Hamosh, Elizabeth J. Nanthakumar, Sheila M. Curristin, Gail Stetten & Clair A. Francomano
3. Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
   Carry R. Cutting, Reed E. Pyeritz, Erik G. Puffenberger, Deborah A. Meyers & Clair A. Francomano
4. Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
   Gail Stetten
5. Shriners Hospital for Crippled Children, Health Sciences University, Portland, Oregon, 97201, USA
   Cheryl L. Maslen, Lynn Y Sakai & Glen M Corson
6. Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, Oregon, 97201, USA
   Lynn Y Sakai

Authors

1. Harry C. Dietz
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2. Carry R. Cutting
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3. Reed E. Pyeritz
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4. Cheryl L. Maslen
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5. Lynn Y Sakai
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6. Glen M Corson
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7. Erik G. Puffenberger
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8. Ada Hamosh
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9. Elizabeth J. Nanthakumar
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10. Sheila M. Curristin
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11. Gail Stetten
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12. Deborah A. Meyers
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13. Clair A. Francomano
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Dietz, H., Cutting, C., Pyeritz, R. et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene.Nature 352, 337–339 (1991). https://doi.org/10.1038/352337a0

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• Received: 20 May 1991
• Accepted: 14 June 1991
• Issue Date: 25 July 1991
• DOI: https://doi.org/10.1038/352337a0

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