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Wednesday 18 May 2005

A number of genes have been implicated and their mutations have been associated with XX sexual developmental abnormalities.

The most important genes controlling the initial phase of gonadal development, identical in females and males, are Wilms’ tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF1).

Four genes are likely to be involved in the subsequent stages of ovarian development (WNT4, DAX1, FOXL2 and RSPO1), but none is yet proven to be the ovarian determining factor.


Three main categories have been used to describe DSD in the 46,XX individual:
- 1) disorders of gonadal (ovarian) development: ovotesticular DSD, previously named true hermaphroditism, testicular DSD, previously named XX males, and gonadal dysgenesis;
- 2) disorders related to androgen excess (congenital adrenal hyperplasia, aromatase deficiency and P450 oxidoreductase deficiency);
- 3) other rare disorders.

- PSMC3IP-associated XX ovarian dysgenesis (21963259)

Nota bene: Changes in nomenclature and The term "disorders of sex development" (DSD) is proposed to substitute the previous term "intersex disorders".

Etiology (Exemples)

- SOX9 duplication
- PSMC3IP mutation in PSMC3IP-associated XX ovarian dysgenesis (21963259)

Open references

- Sex determination and disorders of sex development according to the revised nomenclature and classification in 46,XX individuals. Kousta E, Papathanasiou A, Skordis N. Hormones (Athens). 2010 Jul-Sep;9(3):218-131. PMID: 20688619[Free]


- XX ovarian dysgenesis is caused by a PSMC3IP/HOP2 mutation that abolishes coactivation of estrogen-driven transcription. Zangen D, Kaufman Y, Zeligson S, Perlberg S, Fridman H, Kanaan M, Abdulhadi-Atwan M, Abu Libdeh A, Gussow A, Kisslov I, Carmel L, Renbaum P, Levy-Lahad E. Am J Hum Genet. 2011 Oct 7;89(4):572-9. PMID: 21963259