Table 6

 Genes known to be involved in disorders of sex development: 46,XX

GeneProteinOMIMLocusInheritanceGonadMullerian structuresExternal genitaliaAssociated features/variant phenotypes
ACTH, adrenocorticotropin; AD, autosomal dominant; AR, autosomal recessive; CAH, congenital adrenal hyperplasia; ND, not determined; TF, transcription factor; X, X chrosomal; Y, Y chromosomal.
Chromosomal rearrangements likely to include key genes are included. Modified from Achermann et al88, with permission from the Endocrine Society.
Disorders of gonadal (ovarian) development
SRYTF480000Yp11.3TranslocationTestis or ovotestisMale or ambiguous
SOX9TF60816017q24dup17q24NDMale or ambiguous
Androgen excess
HSD3B2Enzyme2018101p13AROvary+ClitoromegalyCAH, primary adrenal failure, partial androgenisation due to ↑DHEA
CYP21A2Enzyme2019106p21-23AROvary+AmbiguousCAH, phenotypic spectrum from severe salt losing forms associated with adrenal failure to simple virilising forms with compensated adrenal function, ↑17-hydroxyprogesterone
CYP11B1Enzyme2020108q21-22AROvary+AmbiguousCAH, hypertension due to ↑11-deoxycortisol and 11-deoxycorticosterone
POR (P450 oxido-reductase)CYP enzyme electron donor1240157q11.2AROvary+AmbiguousMixed features of 21-hydroxylase deficiency, 17α-hydroxylase/17,20-lyase deficiency and aromatase deficiency; associated with Antley Bixler craniosynostosis
CYP19Enzyme10791015q21AROvary+AmbiguousMaternal androgenisation during pregnancy, absent breast development at puberty, except in partial cases
Glucocorticoid receptorNuclear receptor TF1380405q31AROvary+Ambiguous↑ACTH, 17-hydroxyprogesterone and cortisol; failure of dexamethasone suppression (NB patient heterozygous for a mutation in CYP21)