Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3.
Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.
Geissler
W M
WM
Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065.
Davis
D L
DL
Wu
L
L
Bradshaw
K D
KD
Patel
S
S
Mendonca
B B
BB
Elliston
K O
KO
Wilson
J D
JD
Russell
D W
DW
Andersson
S
S
D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D000595:Amino Acid Sequence; D000735:Androstenedione / Q000378:metabolism; D001483:Base Sequence; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D012734:Disorders of Sex Development / Q000196:embryology / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009928:Organ Specificity; D010641:Phenotype; D017354:Point Mutation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000196:embryology / Q000201:enzymology*; D013739:Testosterone / Q000096:biosynthesis / Q000172:deficiency
D018076:DNA, Complementary; D007527:Isoenzymes; D013739:Testosterone; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases; C045840:testosterone 17 beta-dehydrogenase (NADP+)