FROM GENOTYPE TO PHENOTYPE - MOLECULAR-GE NETIC ANALYSIS IN INTERSEX DISORDERS

The determination of the genetic background of sexual development has not only assisted in the explanation of intersex disorders, but also i n the diagnosis and clinical management of affected individuals. The p ossibilities and limitations of molecular genetic studies can be illus trated by the example of androgen insensitivity syndromes. The search for the underlying mutations within the androgen receptor gene is tech nically possible even for large numbers of patients. The characterizat ion of mutations can be performed with high specificity and sensitivit y. While large gene defects are associated with complete loss of funct ion of the receptor, point mutations with subsequent amino acid change s are responsible for the phenotypic variability of the disease. Type and location of the amino acid substitution may influence the clinical appearance of the individual patient, but the phenotype can be highly variable even with the same underlying mutation. This is probably due to regulation mechanisms within the cell of which the androgen recept or is only one, although important, part. Therefore, results of molecu lar genetic testing have to be interpreted only in connection with cli nical and laboratory findings. Further research will focus on the eluc idation of the cellular mechanisms of androgen action in order to intr oduce the results into the clinical management of patients with androg en insensitivity.