Report of fertility in a woman with a predominantly 46,XY karyotype

[Jamie D]

Report of fertility in a woman with a predominantly 46,XY karyotype in a family with multiple disorders of sexual development
Abstract only - full article at link

Context: We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin fibroblasts (80% 46,XY and 20% 45,X) and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X). -----

Patients: A 46,XY mother who developed as a normal woman, underwent spontaneous puberty, reached menarche, menstruated regularly, experienced two unassisted pregnancies, and gave birth to a 46,XY daughter with complete gonadal dysgenesis. -----

Results: Evaluation of the Y chromosome in the daughter and both parents revealed that the daughter inherited her Y chromosome from her father. Molecular analysis of the genes SOX9, SF1, DMRT1, DMRT3, TSPYL, BPESC1, DHH, WNT4, SRY and DAX1 revealed normal coding sequences in both the mother and daughter. An extensive family pedigree across four generations revealed multiple other family members with ambiguous genitalia and infertility in both phenotypic males and females and the mode of inheritance of the phenotype was strongly suggestive of X-linkage. -----

Conclusions: The range of phenotypes observed in this unique family suggests that there may be transmission of a mutation in a novel sex determining gene or in a gene that predisposes to chromosomal mosaicism.

Source: Artemis is a girl

[pebbles]

wow  that's pretty amazing.

[~RoadToTrista~]

How do they have uteruses?!

[spacial]

It generally seems to be taken as a given that physical gender is determined by the shape of one of the 46th chromazones.

I just find this too neat, too straightforward. If I've learn one thing about humans, it's that nothing is simple and neat.

Sorry if this point is not strictly relevant to the topic, which frankly is outside any area of expertise anyway. But given the seemingly devastating genetic differences that apparently have emerged in this women, that she is a human at all suggests that our simplistic comprehension of genetics is misplaced.

[luna nyan]

Trista - Default development path of mammals is female - presence of Y chromosome stimulates differentiation from female to male.  If the Y chromosome present is faulty in some way and fails to stimulate male sexual differentiation, then the default female pathway develops.  The degree of female development will vary depending on the "disorder"
(Please note that I use disorder here purely in scientific terms of normal expected development - I am not saying that intersexed need to be fixed!)

This type of thing happening gives me hope that some day transition will be a gene therapy type of process, rather than what we have right now.

[Jamie D]

How do they have uteruses?!

Androgen insensitivity syndrome, I guess.

There are untold numbers of phenotypical women who don't find out they are genotypical 46-XY until they are tested for lack of a period, or problems getting pregnant  Then they find out they are 46-XY instead of 46-XX.

The woman who bore the child was "mosaic" - meaning she had, variously, both sets of genes throughout her body.

[TheAetherealMeadow]

The development of uteri is usually inhibited by anti-Mullerian hormone in 46,XY people. In some cases of CAIS, not only are the androgen receptors totally insensitive to androgens, but there is also a lack of anti-Mullerian hormone, so they go on to develop a uterus.

[peky]

Trista - Default development path of mammals is female - presence of Y chromosome stimulates differentiation from female to male.  If the Y chromosome present is faulty in some way and fails to stimulate male sexual differentiation, then the default female pathway develops.  The degree of female development will vary depending on the "disorder"
(Please note that I use disorder here purely in scientific terms of normal expected development - I am not saying that intersexed need to be fixed!)

This type of thing happening gives me hope that some day transition will be a gene therapy type of process, rather than what we have right now.

Since SRY gene and the other downstream genes are Ok, the only way to have a fertile female is by chromosome inactivation. The Y chromosome is inactive, this is called a Barr corpuscle. It happens in all females, one X chromosome has to be inactivated, failure to do so results into intrauterine death or birth defect.