Table 5

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

GeneProteinOMIMLocusInheritanceGonadMullerian structuresExternal genitaliaAssociated features/variant phenotypes
AD, autosomal dominant; AR, autosomal recessive; CAH, congenital adrenal hyperplasia; TF, transcription factor; X, X-linked recessive; Y, Y-linked recessive.
Copyright 2002, The Endocrine Society.
46,XY DSD
Disorders of gonadal (testicular) development: single gene disorders
WT1TF60710211p13ADDysgenetic testis+/−Female or ambiguousWilms tumour, renal abnormalities, gonadal tumours (WAGR, Denys-Drash, and Frasier syndromes)
SF1 (NR5A1)Nuclear receptor TF1847579q33AD/ARDysgenetic testis+/−Female or ambiguousMore severe phenotypes include primary adrenal failure; milder phenotypes have isolated partial gonadal dysgenesis
SRYTF480000Yp11.3YDysgenetic testis or ovotestis+/−Female or ambiguous
SOX9TF60816017q24-25ADDysgenetic testis or ovotestis+/−Female or ambiguousCampomelic dysplasia (17q24 rearrangements milder phenotype than point mutations)
DHHSignalling molecule60542312q13.1ARDysgenetic testis+FemaleThe severe phenotype of one patient included minifascicular neuropathy, other patients have isolated gonadal dysgenesis
ATRXHelicase (?chromatin remodelling)300032Xq13.3XDysgenetic testisFemale, ambiguous or maleα-Thalassaemia, mental retardation
ARXTF300382Xp22.13XDysgenetic testisAmbiguousX-linked lissencephaly, epilepsy, temperature instability
Disorders of gonadal (testicular) development: chromosomal changes involving key candidate genes
DMRT1TF6024249p24.3Monosomic deletionDysgenetic testis+/−Female or ambiguousMental retardation
DAX1 (NR0B1)Nuclear receptor TF300018Xp21.3dupXp21Dysgenetic testis or ovary+/−Female or ambiguous
WNT4Signalling molecule6034901p35dup1p35Dysgenetic testis+AmbiguousMental retardation
Disorders of hormone synthesis or action
LHGCRG protein receptor1527902p21ARTestisFemale, ambiguous or micropenisLeydig cell hypoplasia
DHCR7Enzyme60285811q12-13ARTestisVariableSmith-Lemli-Opitz syndrome: coarse facies, second-third toe syndactyly, failure to thrive, developmental delay, cardiac and visceral abnormalities
STARMitochondrial membrane protein6006178p11.2ARTestisFemaleCongenital lipoid adrenal hyperplasia (primary adrenal failure), pubertal failure
CYP11A1Enzyme11848515q23-24ARTestisFemale or AmbiguousCongenital adrenal hyperplasia (primary adrenal failure), pubertal failure
HSD3B2Enzyme2018101p13.1ARTestisAmbiguousCAH, primary adrenal failure, partial androgenisation due to ↑DHEA
CYP17Enzyme20211010q24.3ARTestisFemale, ambiguous or micropenisCAH, hypertension due to ↑corticosterone & 11-deoxycorticosterone (except in isolated 17,20-lyase deficiency)
POR (P450 oxido-reductase)CYP enzyme electron donor1240157q11.2ARTestisMale or ambiguousMixed features of 21-hydroxylase deficiency, 17α-hydroxylase/17,20-lyase deficiency, and aromatase deficiency; sometimes associated with Antley Bixler craniosynostosis
HSD17B3Enzyme6055739q22ARTestisFemale or ambiguousPartial androgenisation at puberty, ↑androstenedione:testosterone ratio
SRD5A2Enzyme6073062p23ARTestisAmbiguous or micropenisPartial androgenisation at puberty, ↑testosterone:DHT ratio,
AMHSignalling molecule60095719p13.3-13.2ARTestis+Normal malePersistent mullerian duct syndrome (PMDS). Male external genitalia, bilateral cryptorchidism
AMH-ReceptorSerine-threonine kinase transmembrane receptor60095612q13ARTestis+Normal male
Androgen receptorNuclear receptor TF313700Xq11-12XTestisFemale, ambiguous, micropenis or normal malePhenotypic spectrum from complete androgen insensitivity syndrome (female external genitalia) and partial androgen insensitivity (ambiguous) to normal male genitalia/infertility