Identification of a neocentromere in a rearranged Y chromosome with no detectable DYZ3 centromeric sequence.

An 18-year-old woman was evaluated because of primary amenorrhea and hypogonadism. Chromosome analysis from peripheral blood lymphocytes revealed a nonmosaic 46,X,+mar constitution. The marker was shown to be a rearranged Y chromosome consisting of an inverted duplication of the long arm: rea(Y)(qter-q11::q11-qter). Deletion mapping analysis with Y-specific STS showed that the marker lacked Yp and Y-centromeric (DYZ3) sequences, but it was positive for Yq sequences tested. Fluorescence in situ hybridization analysis with Y and X chromosome centromeric and pancentromeric probes showed no hybridization signals. The marker chromosome is present in 100% of the cells; therefore, it is mitotically stable despite the absence of DYZ3 centromeric sequence. Hybridization with CENP-A and CENP-C specific antibodies localized a neocentromere close to the breakpoint.

Idiopathic male pseudohermaphroditism is associated with prenatal growth retardation.

UNLABELLED: About 50% of intersex cases are due to male pseudohermaphroditism, and of these cases, 50% are not clarified aetiologically. The association of idiopathic male pseudohermaphroditism and prenatal growth retardation has been recently reported. The aim of this study was to verify whether there was a difference in weight and/or length at birth between idiopathic and non-idiopathic male pseudohermaphroditism patients. A total of 70 patients with male pseudohermaphroditism were recruited; 35 non-idiopathic and 35 idiopathic. Birth weight and length were converted to z scores, and the severity of genital ambiguity was classified according to Prader grades: less virilized (Prader 1 to 3) and more virilized (Prader 4 or 5). Data were analysed using a Mann-Whitney test, odds ratio and logistic regression analysis. Birth weight (P = 0.028) and length (P = 0.01) z scores were lower in the idiopathic male pseudohermaphroditism group compared to the non-idiopathic group and were also significantly decreased among the less virilized patients, both in the sample as a whole (weight z score, P = 0.002; length z score, P = 0.0008) and in the group of idiopathic patients (weight z score, P = 0.013; length z score, P = 0.007). According to logistic regression analysis, only birth length z score significantly predicted the severity of the genital ambiguity in patients with idiopathic male pseudohermaphroditism ( P = 0.0007). CONCLUSION: There is an association between prenatal growth retardation and male pseudohermaphroditism which may be due to genetic factors not clarified yet or to environmental factors which act early in gestation.