Familial case of 46,XX male and 46,XX true hermaphrodite associated with a paternal-derived SRY-bearing X chromosome.
The human testis-determining gene was recently isolated from a 35 kb region on the human Y chromosome which was present in four sex-reversed individuals, three XX males and one true hermaphrodite. One of the XX males and the true hermaphrodite were sibs. A more detailed molecular analysis of these two patients and their family for Y-DNA sequences including the testis-determining gene, SRY was performed. The father was found to harbor two copies of SRY, one on his Y chromosome and the other on his X chromosome located at Xp22 determined by in situ hybridization. Somatic cell hybrids were generated from peripheral blood lymphocytes. Analysis of Y chromosome-negative somatic cell hybrids from the XX male, the true hermaphrodite and their father, revealed that both the X and Y pseudo-autosomal boundaries were present. The present of both boundaries suggests than an unequal interchange of X and Y material occurred with the cross-over breakpoint located within the X pseudo-autosomal region. The paternal SRY-bearing X chromosome was transmitted to two of his children, a 46 XX true hermaphrodite and a 46,XX male. The presence of SRY on an X chromosome associated with two sex phenotypes strongly suggests that the phenotypic variability was caused by differential inactivation of the SRY-bearing X chromosome, thereby influencing SRY expression.
Abbas
N
N
Immunogénétique Humaine, Institut Pasteur, Paris, France.
McElreavey
K
K
Leconiat
M
M
Vilain
E
E
Jaubert
F
F
Berger
R
R
Nihoul-Fekete
C
C
Rappaport
R
R
Fellous
M
M
D001483:Base Sequence; D015139:Blotting, Southern; D007446:Chromosome Inversion; D003434:Crossing Over, Genetic; D012734:Disorders of Sex Development / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D012732:Sex Determination Analysis; D012733:Sex Differentiation / Q000235:genetics; D013737:Testis / Q000254:growth & development; D014960:X Chromosome