Journal ArticleDOI
Male pseudohermaphroditism caused by mutations of testicular 17β-hydroxysteroid dehydrogenase 3
Wayne M. Geissler,Daphne L. Davis,Ling Wu,Karen D. Bradshaw,S. Patel,Berenice B. Mendonca,Keith O. Elliston,Jean D. Wilson,David W. Russell,Stefan Andersson +9 more
TLDR
Four substitution and two splice junction mutations were identified in the 17βHSD3 genes of five unrelated male pseudohermaphrodites that severely compromised the activity of the 17 β–HSD type 3 isozyme.Abstract:
Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17β–hydroxysteroid dehydrogenase (17β–HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17β–HSD type 3 isozyme that shares 23% sequence identity with other 1 7β–HSD enzymes, uses NADPH as a cofactor, and is expressed predominantly in the testes. The 17βHSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17βHSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17β–HSD type 3 isozyme.read more
Citations
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Journal ArticleDOI
Differential expression of 17beta-hydroxysteroid dehydrogenases types 2 and 4 in human endometrial epithelial cell lines.
TL;DR: Theendometrial epithelial cell lines HEC-1-A and RL95-2 represent a suitable in vitro model for further studies of the differential expression of the major endometrial HSD isozymes, independent of the effect of progesterone.
Journal ArticleDOI
Finding genes involved in human developmental disorders.
TL;DR: Genotype/phenotype comparison and functional analysis of genes responsible for human developmental anomalies will further elucidate pathways of normal and abnormal human development of the skeletal and other organ systems.
Journal ArticleDOI
Biochemical analyses and molecular modeling explain the functional loss of 17β-hydroxysteroid dehydrogenase 3 mutant G133R in three Tunisian patients with 46, XY Disorders of Sex Development.
Roger T. Engeli,Bochra Ben Rhouma,Christoph P. Sager,Maria Tsachaki,Julia Birk,Faiza Fakhfakh,Leila Keskes,Neila Belguith,Alex Odermatt +8 more
TL;DR: Novel compound heterozygous mutations in HSD17B3, composed of the nonsense mutation C206X and the missense mutation G133R, are reported in three Tunisian patients from two non-consanguineous families, indicating an essential role of G133 in the arrangement of the cofactor binding pocket, thus explaining the loss-of-function of 17β-HSD3 mutant G 133R.
Journal ArticleDOI
Molecular determinants of sexual differentiation
TL;DR: The processes ofSexual differentiation have been greatly clarified by molecular biologic discoveries over the past five years and errors in this pathway may be manifested clinically as intersex disorders, and the study of these disorders has helped to further elucidate the molecular mechanisms of sexual differentiation.
Book ChapterDOI
Molecular Biology and Developmental Regulation of the Enzymes Involved in the Biosynthesis and Metabolism of Neurosteroids
TL;DR: It is established that the genes encoding the steroidogenic enzymes are expressed in multiple species, from frogs to human beings, in a developmental, regional, and tissue-specific fashion in the central and peripheral nervous systems.
References
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Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme.
TL;DR: The structure of the sterol 26-hydroxylase cDNA reveals it to be a mitochondrial cytochrome P-450, and blotting experiments revealed that the mRNA for this enzyme is expressed in many tissues and that it is encoded by a low copy number gene in the rabbit genome.
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TL;DR: A dictionary of sites and patterns found in protein sequences, developed, in the last two years, by the author, which is called PROSITE.
Cloning, structure and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase
TL;DR: In this article, the authors used protein sequencing and molecular cloning techniques to isolate and characterize a cDNA encoding the rabbit mitochondrial sterol 26-hydroxylase, which catalyzes the first step in the oxidation of the side chain of sterol intermediates in the biosynthesis of bile acids.