Wednesday, March 01, 2017

How Many Times…

…Have you read a comment that says gender is determined by our chromosomes, if you are XY you have a penis or if you are XX have a vagina. Well they are totally wrong! There are so many other determines gender.

And now they found another thing that determines gender. I just came across this research paper,
A case report of an XX male with complete masculinization but absence of the SRY gene *
Middle East Fertility Society
By Ghalia Abou Alchamata, Marwan Alhlabib, Muhyiddin Issaa
Received 16 November 2009, Accepted 14 December 2009


A 34-year old man with complete masculinization and a history of several years of infertility was referred to us for genetic reviewing. His semen analysis showed azoospermia. Conventional chromosomal analysis indicates a 46,XX karyotype, molecular analyses excluded the presence of SRY (the sex-determining region of the Y chromosome) gene. This case is one of the rare cases reported in the literature in whom testicular differentiation and complete virilization were found in a 46,XX chromosomal constitution, with the absence of SRY gene. This finding suggests that other genes downstream from SRY play an important role in sex determination. Through reporting this rare case and reviewing previous literatures, the aim of this report is to highlight the value of genetically screening all males with azoospermia who present for evaluation of infertility, since the phenotype does not always correlate with the genotype.
4. Discussion

XX male syndrome is a rare syndrome usually occurs as a sporadic event with a frequency of approximately 1/20,000–1/25,000 individuals. The vast majority, about 90%, has SRY detectable in their cells, the remaining 10% are SRY negative (8), although some research suggest a higher figure that reaches up to 20% of the cases (9). The cause of XX male negative for SRY gene is not known. It is well recognized that the presence of the SRY gene determines the sex in mammals by way of directing the sex determination pathway towards male development (10) but the existence of SRY-negative males ruled out the prevailing notion that the mere presence of SRY determines maleness (7), and the development of the testis and normal male genitals in a significant number of SRY-negative 46,XX males gives clue to the existence of other autosomal or X-linked genes in the sex-determining pathway (11). The etiology of development of male phenotype in most of the SRY-negative 46,XX males remains unexplained, researchers 12 and 13 suggested the presence of other mutations (autosomal or X-linked) which could be responsible for testicular determination in the absence of Y sequences. SOX9 and DAX1 genes have recently been proposed to function downstream to SRY gene in male sex determination pathway (14). The reporting of a Mexican family in which two siblings without genital ambiguities were SRY negative (4), suggested that an inherited loss of function mutation in a gene participating in the sex-determining cascade could induce normal male sexual differentiation in the absence of SRY gene. Another possibility for the etiology of maleness in these cases is a downstream gene on the X chromosome in which expression is influenced by X inactivation (15). Lastly, it has been postulated that the sex reversal in these patients is due to a defect on a yet unidentified autosomal or X-linked sex-determining gene (16). If the gene is autosomal, the degree of the male phenotype will be dependent on the extent of the loss or gain of function in the mutant gene. The phenotype in the heterozygotic mutants for X-linked gene will be determined by the ratio of the active and inactive copies of the gene (8). But until date, no clear explanations have been reached. Comprehensive genetic analysis of similar cases may help to detect new gene(s) involved in the sex-determining pathway.

This case is one of the rare cases we examined amongst the 262 patients, who came to our laboratory for genetic reviewing, this SRY-negative XX male have fully mature normal male genitalia with infertility as the main complaint. Cytogenetic and molecular cytogenetic analysis showed only 46,XX cell populations without any numerical or structural chromosomal aberrations. Molecular study was negative for SRY gene and other Y-chromosome sequences. We conclude that the presence of such cases emphasise the importance of genetic evaluation of all infertile couples seeking reproductive assistance since not always the phenotype does correlate with the genotype.
This goes to show you how complicated gender really is, there’re so many variables and many of them are still not known. Just to name a few of the more common intersex conditions; Congenital Adrenal Hyperplasia (CAH), Androgen Insensitivity Syndrome (AIS), 5-alpha-reductase Deficiency, and Mosaic Genetics.

Nature loves diversity.

This morning I am out in Willimantic giving training to a clinic’s staff.

No comments: