POINT MUTATION OF ARG440 TO HIS IN CYTOCHROME P450C17 CAUSES SEVERE 17-ALPHA-HYDROXYLASE DEFICIENCY

被引:57
作者
FARDELLA, CE
HUM, DW
HOMOKI, J
MILLER, WL
机构
[1] UNIV CALIF SAN FRANCISCO, DEPT PEDIAT, SAN FRANCISCO, CA 94143 USA
[2] UNIV CALIF SAN FRANCISCO, METAB RES UNIT, SAN FRANCISCO, CA 94143 USA
[3] UNIV ULM, DEPT PEDIAT 1, D-80975 ULM, GERMANY
关键词
D O I
10.1210/jc.79.1.160
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Genetic disorders in the gene encoding P450c17 cause 17 alpha-hydroxylase deficiency. The consequent defects in the synthesis of cortisol and sex steroids cause sexual infantilism and a female phenotype in both genetic sexes as well as mineralocorticoid excess and hypertension. A 15-yr-old patient from Germany was seen for absent pubertal development and mild hypertension with hypokalemia, high concentrations of 17-deoxysteroids, and hypergonadotropic hypogonadism. Analysis of her P450c17 gene by polymerase chain reaction amplification and direct sequencing showed mutation of codon 440 from CGC (Arg) to CAC (His). Expression of a vector encoding this mutated form of P450c17 in transfected nonsteroidogenic COS-1 cells showed that the mutant P450c17 protein was produced, but it lacked both 17 alpha-hydroxylase and 17,20-lyase activities. To date, 15 different P450c17 mutations have been described in 23 patients with 17 alpha-hydroxylase deficiency, indicating that mutations in this gene are due to random events.
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页码:160 / 164
页数:5
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