title: Structural aspects of the p.P222Q homozygous mutation of HSD3B2 gene in a patient with congenital adrenal hyperplasia.
abstract: Type II 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4)-isomerase (3β-HSD2), encoded by the HSD3B2 gene, is a key enzyme involved in the biosynthesis of all the classes of steroid hormones. Deleterious mutations in the HSD3B2 gene cause the classical deficiency of 3β-HSD2, which is a rare autosomal recessive disease that leads to congenital adrenal hyperplasia (CAH). CAH is the most frequent cause of ambiguous genitalia and adrenal insufficiency in newborn infants with variable degrees of salt losing. Here we report the molecular and structural analysis of the HSD3B2 gene in a 46,XY child, who was born from consanguineous parents, and presented with ambiguous genitalia and salt losing. The patient carries a homozygous nucleotide c.665C>A change in exon 4 that putatively substitutes the proline at codon 222 for glutamine. Molecular homology modeling of normal and mutant 3β-HSD2 enzymes emphasizes codon 222 as an important residue for the folding pattern of the enzyme and validates a suitable model for analysis of new mutations.
authors.affiliation: Center for Molecular Biology and Genetic Engineering, Universidade Estadual de Campinas, SP, Brazil.
authors.forename: Letícia Gori
authors.initials: LG
authors.lastname: Lusa
authors.forename: Sofia Helena Valente de
authors.initials: SH
authors.lastname: Lemos-Marini
authors.forename: Fernanda Caroline
authors.initials: FC
authors.lastname: Soardi
authors.forename: Lucio Fabio Caldas
authors.initials: LF
authors.lastname: Ferraz
authors.forename: Gil
authors.initials: G
authors.lastname: Guerra-Júnior
authors.forename: Maricilda Palandi de
authors.initials: MP
authors.lastname: Mello
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D003062:Codon; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D011375:Progesterone Reductase / Q000235:genetics*
chemical_list: D003062:Codon; D015096:3-Hydroxysteroid Dehydrogenases; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase