Two Prevalent CYP17 Mutations and Genotype-Phenotype Correlations in 24 Brazilian Patients with 17-Hydroxylase Deficiency
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Le résumé fourni par la source
We performed molecular genetic analysis of 24 subjects from 19 families with 17-hydroxylase deficiency in Brazil. Of 7 novel CYP17 mutations, 2 (W406R and R362C) account for 50% and 32% of the mutant alleles, respectively. Both mutations were completely inactive when studied in COS-7 cells and yeast microsomes; however, phenotypic features varied among subjects. Some 46,XY individuals with these genotypes had ambiguous genitalia, and other subjects had normal blood pressure and/or serum potassium. We found mutations W406R and R362C principally in families with Spanish and Portuguese ancestry, respectively, suggesting that two independent founder effects contribute to the increased prevalence of 17-hydroxylase deficiency in Brazil. Mutations Y329D and P428L retained a trace of activity, yet the two individuals with these mutations had severe hypertension and hypokalemia. The 46,XX female with mutation Y329D reached Tanner stage 5, whereas the 46,XY subject with mutation P428L remained sexually infantile. The severity of hypertension, hypokalemia, 17-deoxysteroid excess, and sex steroid deficiency varied, even among patients with completely inactive CYP17 protein(s). Spontaneous sexual development occurred only in 46,XX females with partial deficiencies. We conclude that other factors, in addition to CYP17 genotype, contribute to the phenotype of individual patients with 17-hydroxylase deficiency.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Two Prevalent <i>CYP17</i> Mutations and Genotype-Phenotype Correlations in 24 Brazilian Patients with 17-Hydroxylase Deficiency
- Date Crossref
- 01/01/2004
- Éditeur
- The Endocrine Society
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Associação Paulista de Medicina pays non établi dans la noticeOrganisation à but non lucratif
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Universidade Federal de São Paulo pays non établi dans la noticeUniversité ou école supérieure
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The University of Texas Southwestern Medical Center pays non établi dans la noticeÉtablissement de santé
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Federal University of Sao Paulo Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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University of Texas Southwestern Medical Center (R.J.A.) Department of Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
Associação Paulista de Medicina, Universidade Federal de São Paulo et The University of Texas Southwestern Medical Center, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.