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| MARFAN PHENOTYPE VARIABILITY IN A FAMILY SEGREGATING A MISSENSE MUTATION IN THE EPIDERMAL GROWTH-FACTOR LIKE MOTIF OF THE FIBRILLIN GENE |
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| Author(s): DIETZ HC, PYERITZ RE, PUFFENBERGER EG, KENDZIOR RJ, CORSON GM, MASLEN CL, SAKAI LY, FRANCOMANO CA, CUTTING GR |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 89 Issue: 5 Pages: 1674-1680 Published: MAY 1992 |
| Times Cited: 123 References: 32 |
| Abstract: To examine the associations among fibrillin gene mutations, protein function, and Marfan syndrome phenotype, we screened for alterations in the fibrillin coding sequence in patients with a range of manifestations and clinical severity. A cysteine to serine substitution at codon 1409 (C1409S) was identified in an epidermal growth factor (EGF)-like motif from one fibrillin allele which segregates with the disease phenotype through three generations of a family affected with the Marfan syndrome. This alteration was not observed in 60 probands from other families or in 88 unrelated normal individuals. The altered cysteine is completely conserved in all EGF-like motifs identified in fibrillin, and in all proteins that contain this motif. These observations strongly indicate that C1409S is the disease-producing mutation in this family. The phenotype of individuals carrying C1409S varied widely with respect to onset of disease, organ-system involvement, and clinical severity; certain affected adults were unaware of their status before being diagnosed through this investigation. We conclude that fibrillin gene defects cause familial Marfan syndrome, that mutations in the EGF-like motif of the fibrillin gene are not uniformly associated with severe disease, and that fibrillin genotype is not the sole determinant of Marfan phenotype. |
| Document Type: Note |
| Language: English |
Addresses:
1. JOHNS HOPKINS UNIV, SCH MED, DEPT PEDIAT, DIV PEDIAT CARDIOL, BALTIMORE, MD 21205 USA
2. JOHNS HOPKINS UNIV, SCH MED, CTR MED GENET, DEPT PEDIAT, BALTIMORE, MD 21205 USA
3. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA
4. OREGON HLTH SCI UNIV, DEPT MOLEC & MED GENET & MED, PORTLAND, OR 97201 USA
5. OREGON HLTH SCI UNIV, DEPT BIOCHEM & MOLEC BIOL, PORTLAND, OR 97201 USA
6. SHRINERS HOSP CRIPPLED CHILDREN, PORTLAND, OR USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: HT983 |
| ISSN: 0021-9738 |
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