title: Six new cases confirm the clinical molecular profile of complete combined 17α-hydroxylase/ 17,20-lyase deficiency in Brazil.
abstract: In 2004, Costa-Santos and cols. reported 24 patients from 19 Brazilian families with 17α-hydroxylase deficiency and showed that p.W406R and p.R362C corresponded to 50% and 32% of CYP17A1 mutant alleles, respectively. The present report describes clinical and molecular data of six patients from three inbred Brazilian families with 17α-hydroxlyse deficiency. All patients had hypogonadism, amenorrhea and hypertension at diagnosis. Two sisters were found to be 46,XY with both gonads palpable in the inguinal region. All patients presented hypergonadotrophic hypogonadism, with high levels of ACTH (> 104 ng/mL), suppressed plasmatic renin activity, low levels of potassium (< 2.8 mEq/L) and elevated progesterone levels (> 4.4 ng/mL). Three of them, including two sisters, were homozygous for p.W406R mutation and the other three (two sisters and one cousin) were homozygous for p.R362C. The finding of p.W406R and p.R362C in the CYP17A1 gene here reported in additional families, confirms them as the most frequent mutations causing complete combined 17α-hydroxylase/17,20-lyase deficiency in Brazilian patients.
authors.affiliation: Center for Molecular Biology and Genetic Engineering, Universidade Estadual de Campinas, SP, Brazil.
authors.forename: Daiane Rodrigues Barbosa
authors.initials: DR
authors.lastname: Belgini
authors.forename: Maricilda Palandi de
authors.initials: MP
authors.lastname: Mello
authors.forename: Maria Tereza Matias
authors.initials: MT
authors.lastname: Baptista
authors.forename: Daniel Minutti de
authors.initials: DM
authors.lastname: Oliveira
authors.forename: Fernanda Canova
authors.initials: FC
authors.lastname: Denardi
authors.forename: Heraldo Mendes
authors.initials: HM
authors.lastname: Garmes
authors.forename: Oswaldo da Rocha
authors.initials: Oda R
authors.lastname: Grassiotto
authors.forename: Cristina Laguna
authors.initials: CL
authors.lastname: Benetti Pinto
authors.forename: Antonia Paula
authors.initials: AP
authors.lastname: Marques-de-Faria
authors.forename: Andréa Trevas
authors.initials: AT
authors.lastname: Maciel-Guerra
authors.forename: Gil
authors.initials: G
authors.lastname: Guerra-Júnior
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000235:genetics*; D000483:Alleles; D001938:Brazil; D005260:Female; D006801:Humans; D009154:Mutation; D010375:Pedigree; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase