CLINICAL TRAITS AND MOLECULAR FINDINGS IN 46,XX MALES

46,XX maleness is characterized by the presence of testicular developm ent in subjects who lack a Y chromosome. The majority of affected pers ons have normal external genitalia, but 10-15% show various degrees of hypospadias. Several hypotheses have been proposed to explain the eti ology of this constitution: translocation of the testis-determining fa ctor (TDF) from the Y to the X chromosome, mutation in an autosomal or X chromosomal gene which permits testicular determination in the abse nce of TDF, and undetected mosaicism with a Y-bearing cell line. We re port the phenotypic data and results of molecular analyses performed i n six sporadic Mexican males with 46,XX karyotype. Molecular studies r evealed Yp sequences in two individuals (ZFY+ SRY+) with different phe notypes, a third one presented with a smaller segment of Yp (ZFY- SRY) and complete virilization, while the remaining three were Y-negative and showed hypospadias. In all subjects a hidden mosaicism with a Y-b earing cell line was ruled out due to the absence of Y-centromeric seq uences. Our data demonstrate that the phenotype does not always correl ate with the presence or absence of Y-sequences in the genome, and con firm that 46,XX maleness is a genetically heterogeneous condition.