Molecular Characterization of Chromosomal Breakpoints

The molecular basis of human malformation syndromes is still largely unknown. Some are caused by mutations in genes controlling important developmental processes like SOX-9, Gli 3, or PAX-6. Mutations in these genes result in Campomelic dysplasia, Greig Cephalopolysyndactyly syndrome and Aniridia respectively. Identification of these desease genes has been guided by cytogenetically balanced chromomal aberrations in patients with the respective syndromes. The aim of the present project is to identify the gene for Nail Patella Syndrome (NPS) by analysis of the breakpoint region from the only yet known NPS patient with a balanced t(9/17) (q34;q25) translocation. NPS is characterized by hypo- or aplasia of nails, absent or hypoplastic patella, and iliac horns (a form of exostosis). About 30% of patients have nephropathy. Cloning of the NPS gene will not only give insight into aspects of skeleton development but may also clarify the aitology and pathogenesis of more common non-syndromic forms of nephropathy. A further aim of our study is to identify genes from chromosomal breakpoints from carries of balanced chromosomal aberrations with various forms of mal-formations and/or mental retardation which can presently not be assigned to a known genetic syndrome. This will result in the identification of candidate genes for malformation and mental retardation.