Global analysis of gene expression in inherited human craniosynostoses.

• Grant number: 00/07960-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2000
• End date: April 30, 2003
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Maria Rita dos Santos e Passos Bueno
• Grantee: Todd Stephen Zorick
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Inherited autosomal dominant craniosynostoses are common congenital human birth defects, which often require multiple corrective craniofacial surgeries for treatment. Recently, many of these diseases have been mapped to genes for FGFR1-3, particularly in the extracellular ligand binding domain of these transmembrane tyrosine kinase receptor proteins. However, considerable overlap among the clinical symptoms and the causative mutations has prevented a clear understanding of the pathogenesis and prognosis of these conditions. We propose to use skin biopsy samples of patients with craniosynostoses to culture human fibroblasts using established techniques. These cultured fibroblasts will then be analyzed for global mRNA expression by the techniques of SAGÉ and cDNA microarray with the aim of finding genes differentially regulated in the various craniosynostoses in comparison to normal Controls. Patterns of gene expression changes observed in the syndromes will be correlated relative to normal subject Controls and compared to both phenotypic and genotypic information among the craniosynostoses themselves. By this analysis, we hope to be able to improve the understanding of the pathogenesis of these syndromes, to aid in the diagnosis of patients, and to provide some hope for improved prognosis and treatment of affected individuals. (AU)