Nonrandom inactivation of the Y-bearing X chromosome in a 46,XX individual: evidence for the etiology of 46,XX true hermaphroditism.
We previously reported a subject with 46,XX true hermaphroditism who had a 46,X,del(X) karyotype and Y-chromosomal sequences in genomic DNA. We hypothesized that the Y-chromosomal sequences were translocated to the deleted X chromosome and that the incomplete testis determination of this individual was the result of inactivation of the translocated X chromosome. In situ hybridization studies demonstrated that the Y-chromosomal sequences were located on the distal portion of the short arm of the deleted X chromosome. Investigation of the replication of the X chromosome, using a modified R-banding technique and localization of Y-chromosomal sequences by in situ hybridization, showed that the translocated X chromosome was late replicating in all 100 EBV-transformed lymphoblasts that were examined. By contrast, when cells from a subject with 46,XX maleness were studied, the translocated X chromosome was late replicating in only 21 of 47 cells. As the late-replicating X chromosome is presumed to be the inactive X chromosome, selection of cells in which the Y-bearing X chromosome has been inactivated may play a role in the incomplete testis determination in subjects with "Y-positive" 46,XX true hermaphroditism.
Fechner
P Y
PY
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Rosenberg
C
C
Stetten
G
G
Cargile
C B
CB
Pearson
P L
PL
Smith
K D
KD
Migeon
C J
CJ
Berkovitz
G D
GD
D002874:Chromosome Mapping; D012734:Disorders of Sex Development / Q000235:genetics*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007621:Karyotyping; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D010053:Ovary; D012729:Sex Chromosome Aberrations; D013737:Testis; D014960:X Chromosome; D014998:Y Chromosome