Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a homozygous 25 BP duplication (NT 4157-4181) at exon 5 in the CYP17 resulting in a premature stop codon predicted by molecular modeling.
Arq Bras Endocrinol Metabol
; 52(8): 1317-20, 2008 Nov.
Article
en En
| MEDLINE
| ID: mdl-19169487
ABSTRACT
Combined 17alpha-hydroxylase/17,20-lyase deficiency is a rare, autosomal recessive form of congenital adrenal hyperplasia characterized by the coexistence of hypertension, caused by the hyperproduction of mineralocorticoid precursors and DSD in males and sexual infantilism in females, due to impaired production of sex hormones. Several CYP17 mutations resulting in 17alpha-hydroxylase/17,20-lyase deficiency have been reported previously. In the present study, we described a novel CYP17 mutation in two Brazilian sisters with primary amenorrhea, 46,XY karyotype, high basal levels of progesterone (3.4-4.9 ng/mL) and hypokalemic hypertension born to consanguineous parents. After PCR and automatic sequencing of CYP17 coding region, 25 bp duplication at exon 5 was found in the patients. This duplication started at codon 318 resulting in a premature stop codon at position 320 resulting in an ineffective and truncated protein and in accordance with the molecular modeling of P450c17. Therefore we expanded the repertoire of CYP17 mutations describing the largest duplication found in this gene in both sisters, with a clinical phenotype of combined 17alpha-hydroxylase/17,20-lyase deficiency and emphasizes the importance of the P450c 17 molecular modeling to predict the functional effect of these mutations.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Esteroide 17-alfa-Hidroxilasa
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Exones
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Hiperplasia Suprarrenal Congénita
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Codón sin Sentido
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Duplicación de Gen
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Modelos Genéticos
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Female
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Humans
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Male
Idioma:
En
Revista:
Arq Bras Endocrinol Metabol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Brasil