Substitution mutation C268Y causes 17 beta-hydroxysteroid dehydrogenase 3 deficiency.
The 17 beta-hydroxysteroid dehydrogenase (HSD) type 3 isozyme catalyzes the conversion of androstenedione to testosterone in the testis. Deleterious mutations in the HSD17B3 gene cause undermasculinization in genetic males attributable to impaired testosterone biosynthesis. Hence, a hallmark of this autosomal recessive disorder is a decreased plasma testosterone-to-androstenedione ratio. Here, a novel C268Y substitution mutation in exon 10 of the HSD17B3 gene, in a subject with 17 beta-HSD 3 deficiency, is reported. Reconstitution experiments with recombinant protein reveal that substitution of tyrosine for cysteine at position 268 of 17 beta-HSD type 3 abrogates the enzymatic activity. This finding brings to 20 the number of mutations in the HSD17B3 gene that cause male undermasculinization.
Lindqvist
A
A
The Department of Obstetrics-Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.
Hughes
I A
IA
Andersson
S
S
D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D019943:Amino Acid Substitution; D000735:Androstenedione / Q000097:blood; D001483:Base Sequence; D003241:Consanguinity; D005091:Exons; D005808:Genes, Recessive; D006801:Humans; D007006:Hypogonadism / Q000201:enzymology / Q000235:genetics*; D007223:Infant; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007621:Karyotyping; D008297:Male; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014162:Transfection
D007527:Isoenzymes; D011994:Recombinant Proteins; D013739:Testosterone; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases