Semaphorin3E and CHD7 signalling pathways in the control of olfaction and reproduction: link for Kallmann and CHARGE syndromes?

CHARGE syndrome is a complex genetic disease characterized by many abnormalities of the body; these include heart, ear, eye and growth defects. In addition to the main symptoms, patients very often suffer of olfaction and reproductive problems, features that are common of other 2 diseases, Idiopathic Hypogonadotropic Hypogonadism (IHH) and Kallmann Syndrome (KS). The life expectancy of patients affected by CHARGE varies between 5 days and 46 years, with the highest rate of mortality during the first 5 years of life. The genes found mutated are so far only two: CHD7 and SEMA3E. The first, which regulates the expression of other genes, has been found mutated in the majority of CHARGE syndrome cases but also in some patients affected by IHH/KS, strongly supporting a link in the aetiopathogenesis of these diseases. The second, which encodes for a protein important to guide nerve cells during foetal development, has been found mutated so far only in 2 patients affected by CHARGE. However, no direct link has been shown between these 2 genes nor it has been studied whether SEMA3E is involved in the control of reproduction and olfaction during development. Thus, we will apply animal and cellular models to elucidate the role of these 2 proteins during development and to understand their possible contribution to the olfaction and reproductive abnormalities of CHARGE and IHH/KS patients.