LAUSR

Background The comparative role of heredity in the etiology of schizophrenic disorders is estimated as 60-70%, other 30-40% is the share of the environment. However, modern molecular-genetic technologies, including full-genomic, are not able to explain more than 10-15% of the general hereditary components of this multiple-factor disease. One of the main resources of disclosing "missing heritability" is connected with the schizophrenia phenotype, study of clinical polymorphism of schizophrenia and comorbid with it hereditary diseases. Methods For 209 families of patients with different forms of schizophrenia (F20 according to ICD-10) by means of the genealogical method family trees with identification of state of mental and physical health of relatives of the first degree of relationship were made. If hereditary diseases being suspected, biochemical investigations with identification of metabolites, molecular-genetic (with testing of genetic polymorphisms) investigations were carried out. Results Identification of the role of genetic factors in developing of diseases of the noninfectious nature to which schizophrenic disorders belong, through detection of associations of such diseases with Mendelian characters in families showed the following. Schizophrenia and hereditary Mendelian recessive disease with disturbance of the gene coding Cu-transporting ATPase - Wilson-Konovalov illness (hepatocerebral dystrophy). Schizophrenia and hereditary Mendelian dominant disease (with complete penetrance and varying expressivity of the gene FBN1 (fibrillin 1) - the peculiar Mass-phenotype of the proband and his relatives in the area of the father. Schizophrenia and Leiden mutation (predisposition to thrombosis, thrombophilia) with molecular-genetic investigation of polymorphism of Arg506Gln in the gene of V factor of coagulation. The heterozygotic carriage (G/A genotype) was found. Schizophrenia with manifestations of the velocardiofacial syndrome and existence of polymorphisms of alleles of Val 158Met and rs4680 of the gene COMT as well as CYP2D6 gene polymorphisms. Discussion For schizophrenic disorders as diseases with family history and blunted phenotype which do not conform Mendelian patterns of inheritance in which complex interaction of many pathogenic genes with environmental factors takes place, identification of comorbid with them hereditary (chromosomal and gene) diseases gives the chance of the differentiated clinical diagnostics, prediction of course and development, treatment and outcome of the disease for the specific patient as well as possibility of primary prevention in families.