Familial Primary Amenorrhea Due to Testicular Feminization: A Human Gene Affecting Sex Differentiation.

Abstract

A female patient with "male pseudohermaphroditism with feminizing testes" had a 46/XY chromosomal constitution, a fact confirming clinical and genetic deductions drawn by previous investigators largely on the basis of pedigree data, and in accord with recent brief reports on the chromosome condition in other such patients. A detailed chromosomal analysis is provided. Some previous cases having similar clinical manifestations had been recognized by previous workers as being caused either by an autosomal dominant or a sex-linked recessive genetic defect. Analysis of pedigrees from similar cases demonstrates the causative gene defect to be not strongly linked to either of 2 sex-linked genes, hemophilia and color blindness. Hence, it is probably autosomal. Of particular importance is the finding that in the family of this patient, all female transmitters of the defect for whom data were available exhibited a delayed menarche of approximately 8 years. This situation has been rarely noted previously, and requires study as to its universal accompaniment of this condition. It is evident that in the present case the presence of this gene in heterozygous condition in an XX individual causes delay of menarche, while in an XY individual it results in suppression of the male characteristics and a partial development of female traits. It is pointed out that more than one gene locus might be able to produce clinical effects like those here described. Study of the action of such genes appears highly important to problems of human development.