Consequences of mutations/deletions and duplications/translocations of genes involved in gonadal differentiation
| Chromosome location | Gonadal development | Associated disorder | Sex reversal/genital ambiguity | Müllerian development | |
|---|---|---|---|---|---|
| WAGR, Wilms’ tumour, aniridia, genitourinary anomalies, mental retardation; Denys-Drash (exonic mutations) WT, diffuse mesangial sclerosis; Frasier (intronic mutations) no WT, focal segmental glomerulosclerosis. Other abbreviations as for fig 1. | |||||
| Gene mutation or deletion (loss of function) | |||||
| WT1 | 11p13 | Dysgenesis (♀ and ♂) | WAGR syndrome | Genital ambiguity (♂) | Variable (♂) |
| Denys-Drash syndrome | Sex reversal or genital ambiguity (♂) | Variable (♂) | |||
| Frasier syndrome | Sex reversal (♂) | Yes (♂) | |||
| SF1 | 9q33 | Dysgenesis (♂) | Adrenal failure | Sex reversal (♂ | Yes (♂) |
| SRY | Yp11.3 | ♂→ ovary | Sex reversal or genital ambiguity (♂) | ♂ (variable) | |
| DAX1 | Xp21 | ♂ Dysgenesis | Adrenal failure and hypogonadotrophic hypogonadism/impaired spermatogenesis | No | No |
| SOX9 | 17q24.3–25.1 | ♂ Dysgenesis or ovary/ovotestis | Campomelic dysplasia | Sex reversal or genital ambiguity (♂) | Variable |
| AMH | 19p 13.3–13.2 | Normal | Yes (♂) | ||
| Gene duplication or translocation (gain of function) | |||||
| SRY Y fragment translocation | Yp11.3 | ♀→ testis | Sex reversal or genital ambiguity (♀) | No | |
| DAX1 duplication | dupXp21 | ♂ Dysgenesis or ovary/ovotestis | Sex reversal or genital ambiguity (♂) | Variable | |
| Wnt 4 duplication | Dup 1p35 | ♂ Dysgenesis | Genital ambiguity (♂) | Yes | |
| SOX9 duplication | dup17q24.3–25.1 | ♀→ Testis | Genital ambiguity (♀) | No | |