THE MOLECULAR BASIS OF ORAL-FACIAL-DIGITAL TYPE I SYNDROME

Oral-facial-digital syndromes (OFDs) are a heterogeneous group of developmental disorders of which at least nine different forms have been described to date. The different forms are very similar from a clinical point of view and it may be difficult to ascertain the exact subtype. The only welldefined form is OFD type I (OFDI), which can be recognized for the distinctive mode of inheritance and for the presence of polycystic kidney. We have recently identified the causative gene, OFD1, and proved by mutation analysis its role in this genetic disorder. The identification of the gene responsible for OFDI has already provided an important tool for the genetic counseling and a molecular test is now available to patients and clinicians for OFDI diagnosis and prenatal testing. To determine the extent of the involvement of the OFD1 gene in OFDs, and to better define both the clinical spectrum of Oral-facial-digital type 1 syndrome and the actual number of different OFDs we propose to perform mutation analysis in a large collection of patients including also OFD patients with more general signs of oral-facial-digital syndrome. Preliminary results suggest that OFD1 might have a role in diverse cellular functions involving cell cycle progression, cellular proliferation and differentiation. To verify our hypothesis we propose functional studies which will be valuable towards the understanding of the molecular mechanisms underlying OFDI and oral-facial-digital syndromes in general.