A seven-year-old girl with a Y chromosome is providing new clues about a possible 鈥渕aster switch鈥� of maleness.
The girl has the normal chromosome count 鈥� 46 鈥� and should be male. Other children who have the male sex chromosome but do not appear to be boys have been found to have gene mutations that temper the Y chromosome鈥檚 effects. However this child doesn鈥檛 have ambiguous gonads, shrivelled testes or other developmental defects. She instead has a normal vagina, cervix and set of ovaries.
A team led by , of University Children鈥檚 Hospital in Zurich, Switzerland, thinks the patient鈥檚 normalcy is due to mutations in a poorly understood gene on chromosome 17 called CBX2.
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The child鈥檚 unique condition might not have been discovered were it not for tests performed before birth to check for major genetic defects, such as an extra copy of chromosome 21 that causes Down鈥檚 syndrome. Those tests came up negative and indicated the child would be a boy.
Gene shut-down
When a girl with normal sex organs was born, doctors started scratching their heads. Most females with a Y chromosome have underdeveloped gonads that are prone to developing tumours and usually removed. However, when surgeons operated with the intention of removing the gonads they found normal-looking ovaries in the girl, and took only a tissue sample. This sample, too, looked normal.
Experiments in human cells suggest that the mutations in CBX2 shut off a gene critical for male sexual development, called SRY.
Previous research has shown that mice lacking CBX2 are sterile, but Biason-Lauber says it鈥檚 too early to tell whether her team鈥檚 patient will be infertile as well.
鈥淚t is quite possible that the ovaries won鈥檛 function well,鈥� says , a paediatric endocrinologist at University College London鈥檚 Institute of Child Health.
鈥�CBX2 is a predictable and genuine part of the jigsaw puzzle of early human sex development,鈥� Achermann adds. 鈥淭his gene has been on the agenda for human sex development, but it鈥檚 quite important that a case has now been reported.鈥�
Journal reference: (DOI: 10.1016/j.ajhg.2009.03.016)
