title: A New Homozygous Frameshift Mutation in the HSD3B2 Gene in an Apparently Nonconsanguineous Italian Family.
abstract: BACKGROUND
  3β-Hydroxysteroid dehydrogenase (3β-HSD) deficiency is a rare cause of congenital adrenal hyperplasia (CAH) caused by inactivating mutations in the HSD3B2 gene.
  
  
  METHODS
  We report the molecular and structural analysis of the HSD3B2 gene in a 46,XY child born to apparently nonconsanguineous parents and presenting ambiguous genitalia and salt wasting. The steroid profile showed elevated concentrations of 17-hydroxyprogesterone, androstenedione, ACTH and plasma renin, but normal values of cortisol and dehydroepiandrosterone sulfate. Unexpectedly, plasma aldosterone was high. For structural and functional analyses, the three-dimensional structure of 3β-HSD2 was modeled using the crystal structure of the short-chain dehydrogenase Gox2253 from Gluconobacter oxydans as a template.
  
  
  RESULTS
  The direct DNA sequence of the child revealed a new homozygous frameshift mutation in exon 4 of the HSD3B2 gene, a single nucleotide deletion at codon 319 [GTC(Val)x2192;GC], yielding premature stop codon in position 367. Molecular homology modeling and secondary structure predictions suggested that the variant sequence might both alter the substrate-binding cleft and compromise the overall stability of the enzyme.
  
  
  CONCLUSIONS
  We have described the first HSD3B2 gene mutation in the Italian population and analyzed its effect in the context of the 3β-HSD2 structure and function.
authors.forename: Carla
authors.initials: C
authors.lastname: Bizzarri
authors.forename: Arianna
authors.initials: A
authors.lastname: Massimi
authors.forename: Luca
authors.initials: L
authors.lastname: Federici
authors.forename: Antonio
authors.initials: A
authors.lastname: Cualbu
authors.forename: Sandro
authors.initials: S
authors.lastname: Loche
authors.forename: Lorenza
authors.initials: L
authors.lastname: Bellincampi
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Marco
authors.initials: M
authors.lastname: Cappa
authors.forename: Ottavia
authors.initials: O
authors.lastname: Porzio
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000735:Androstenedione / Q000097:blood; D005190:Family; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007231:Infant, Newborn; D007558:Italy; D008297:Male; D011375:Progesterone Reductase / Q000737:chemistry / Q000235:genetics*; D000072417:Protein Domains; D012083:Renin / Q000097:blood; D013329:Structure-Activity Relationship
chemical_list: D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D012083:Renin