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| MARFAN-SYNDROME CAUSED BY A RECURRENT DENOVO MISSENSE MUTATION IN THE FIBRILLIN GENE |
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| Author(s): DIETZ HC, CUTTING GR, PYERITZ RE, MASLEN CL, SAKAI LY, CORSON GM, PUFFENBERGER EG, HAMOSH A, NANTHAKUMAR EJ, CURRISTIN SM, STETTEN G, MEYERS DA, FRANCOMANO CA |
| Source: NATURE Volume: 352 Issue: 6333 Pages: 337-339 Published: JUL 25 1991 |
| Times Cited: 692 References: 22 |
| 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 variability 1. Linkage studies have mapped the Marfan locus to chromosome 15q15-21.3 (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 microfibril 4), immunohistopathological quantification of the protein in skin and fibroblast culture 5, 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 cloned 6 and mapped by in situ hybridization to chromosome 15 (ref. 7). Here we report that the fibrillin gene is linked to the Marfan phenotYPe (theta = 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: DIETZ, HC (reprint author), JOHNS HOPKINS UNIV, SCH MED, DEPT PEDIAT, DIV PEDIAT CARDIOL, BALTIMORE, MD 21205 USA |
Addresses:
1. OREGON HLTH SCI UNIV, SHRINERS HOSP CRIPPLED CHILDREN, PORTLAND, OR 97201 USA
2. OREGON HLTH SCI UNIV, DEPT BIOCHEM & MOLEC BIOL, PORTLAND, OR 97201 USA
3. JOHNS HOPKINS UNIV, SCH MED, DEPT PEDIAT, CTR MED GENET, BALTIMORE, MD 21205 USA
4. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, CTR MED GENET, BALTIMORE, MD 21205 USA
5. JOHNS HOPKINS UNIV, SCH MED, DEPT GYNECOL & OBSTET, CTR MED GENET, BALTIMORE, MD 21205 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: FY289 |
| ISSN: 0028-0836 |
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