Genetic linkage of the marfan syndrome, ectopia lentis, and congenital contractural arachnodactyly to the fibrillin genes on chromosomes 15 and 5

Peter A. Famdon,Birmingham Maternity Hospital, Birmingham, United Kingdom; Maureen Boxer, Ninewells Medical School, Dundee, United Kingdom; David J.H. Brock, Caroline Hayward. and Marion Keston, University of Edinburgh, Edinburgh, United Kingdom; Dianna M. Milewicz, University of Texas, Houston; Peter H. Byers, University of Washington, Seattle; Andrea Superti-Furga, University of Zurich, Zurich, Switzerland; Rajkumar S. Ramesar, University of Cape Town Medical School, Cape Town, South Africa; Margaret Anne Davee and David D. Weaver. Indiana University. Indianapolis; Stephen Wainer. University of Witwatersrand, Johannesburg, South Africa; and Randi Kramer-Fox, Cornell Medical Center~ New York.

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Abstract

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. 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). 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, 1025.6:1). 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. 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. (N Engl J Med 1992;326:905–9.).

Original languageEnglish (US)
Pages (from-to)905-909
Number of pages5
JournalNew England Journal of Medicine
Volume326
Issue number14
DOIs
StatePublished - Apr 2 1992

ASJC Scopus subject areas

  • Medicine(all)

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    Peter A. Famdon,Birmingham Maternity Hospital, Birmingham, United Kingdom; Maureen Boxer, Ninewells Medical School, Dundee, United Kingdom; David J.H. Brock, Caroline Hayward. and Marion Keston, University of Edinburgh, Edinburgh, United Kingdom; Dianna M. Milewicz, University of Texas, Houston; Peter H. Byers, University of Washington, Seattle; Andrea Superti-Furga, University of Zurich, Zurich, Switzerland; Rajkumar S. Ramesar, University of Cape Town Medical School, Cape Town, South Africa; Margaret Anne Davee and David D. Weaver. Indiana University. Indianapolis; Stephen Wainer. University of Witwatersrand, Johannesburg, South Africa; and Randi Kramer-Fox, Cornell Medical Center~ New York. (1992). Genetic linkage of the marfan syndrome, ectopia lentis, and congenital contractural arachnodactyly to the fibrillin genes on chromosomes 15 and 5. New England Journal of Medicine, 326(14), 905-909. https://doi.org/10.1056/NEJM199204023261401