TY - JOUR
T1 - Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene
AU - Dietz, Harry C.
AU - Cutting, Carry R.
AU - Pyeritz, Reed E.
AU - Maslen, Cheryl L.
AU - Sakai, Lynn Y.
AU - Corson, Glen M.
AU - Puffenberger, Erik G.
AU - Hamosh, Ada
AU - Nanthakumar, Elizabeth J.
AU - Curristin, Sheila M.
AU - Stetten, Gail
AU - Meyers, Deborah A.
AU - Francomano, Clair A.
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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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U2 - 10.1038/352337a0
DO - 10.1038/352337a0
M3 - Article
C2 - 1852208
AN - SCOPUS:0025886783
SN - 0028-0836
VL - 352
SP - 337
EP - 339
JO - Nature
JF - Nature
IS - 6333
ER -