Open Access Research article

A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

Zizhen Yao1, Jochen C Jaeger17, Walter L Ruzzo12, Cecile Z Morale38, Mary Emond4, Uta Francke5, Dianna M Milewicz6, Stephen M Schwartz3 and Eileen R Mulvihill39*

Author Affiliations

1 Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA

2 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA

3 Department of Pathology, University of Washington, Seattle, Washington 98195, USA

4 Department of Biostatistics, University of Washington, Seattle Washington 98195, USA

5 Departments of Genetics and Pediatrics, Stanford University, Stanford, CA 94305-5323, USA

6 University of Texas Medical School at Houston, 6431 Fannin, MSB 1.614, Houston, TX 77030, USA

7 Hamilton Robotics, Via Crusch 8, Bonaduz, Switzerland

8 Trubion Pharmaceuticals Inc., Seattle, Washington 98121, USA

9 PO Box 33, Villanueva, NM 87583, USA

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BMC Genomics 2007, 8:319  doi:10.1186/1471-2164-8-319

Published: 12 September 2007



Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms.


We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR.


Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value < 3 × 10-6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status). An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.