Researchers' Proposals
Sólyom, J.:
Genetic background of disorders in sexual differentiation
Semmelweis University, II. Department of Pediatrics, H-1094 Budapest, Tūzoltó u.7-9. HUNGARY
Sexual differentiation involves a cascade of events initiated by the presence of the SRY gene on the Y chromosome, which causes the indifferent gonad to develop into a testis. Hormonal products of the testis control the sexual differentiation of the developing fetus. Testosterone is necessary for masculinization of external genitalia. The androgen receptor mediates the action of testosterone. Lack or abnormality of SRY gene result in gonadal dysgenesis. Mutations of the androgen receptor gene cause undermasculinization of the genetic male fetus.
To investigate the genotype-phenotype correlation in patients with gonadal dysgenesis (Turner-syndrome, complete and partial gonadal dysgenesis), the presence of Y-chromatin and the genomic structure of the SRY-gene will be examined by FISH and PCR. To investigate the genotype-phenotype correlation in patients with androgen insensitivity syndrome, the genomic structure of the androgen receptor gene will be examined by SSCP and sequence determination.
We plan to construct a national database of patients to be involved in this study. Cytogenetic and molecular genetic methods will be introduced for investigation of biological samples derived from these patients. Interrelationships of clinical and laboratory data will be analyzed.