1001 - Reproductive Genetics

Question 1

What is the SRY Gene? What is its function?

Answer 1

Sex determining region of the Y chromosome - AKA Testis Determining factor. Necessary for initiation of male-specific and suppression of female-specific pathways, including secretion of Mullerian Inhibiting Substance and expression of testosterone.

Question 2

How can an XY person be female? How can XX be male?

Answer 2

If SRY gene is mutated to the extent of inactivation, XY people will develop as females with gonadal dysgenesis - no secondary sexual characteristics, menstruation and ‘streak gonads’ otherwise entirely female “Swyer Syndrome”. If it is translocated to X chromosome, males can be XX.
Could also have androgen insensitivity syndrome.

Question 3

What are the two broad pathways involved in ‘androgenous presentation’? How do they present?

Answer 3

Pathways leading to disrupted reproductive tissues and processes - present as infertile.
Pathways leading to disrupted normal endocrine function - present with metabolic disruptions.

Question 4

Briefly outline the intersexes

Answer 4

1/4000 newborns with ambiguous genetalia, leading to infertility, genital abnormalities and gender mis-assignment. Many aetiologies can lead to the same outcome, so management depends on precise pathophysiology for that condition.

Question 5

Briefly outline androgen insensitivity

Answer 5

Gene coding for androgen receptor has an inactivating mutation in an XY individual. 1/65,000 males. Have female external genitalia with internal testes.

Question 6

Briefly outline adrenal hyperplasia

Answer 6

Deficiency in enzyme of cortisol biosynthesis leads to accumulation of cholesterol precursors that get shunted to sex steroids.
95% due to 21 Hydroxylase deficiency.
Present at birth with salt-wasting, simple virilizing. Or later with hirsuitism, precocious puberty, amenorrhea and infertility.