Clinical, hormonal, and molecular genetic characteristics of patients with Р450с17 (17a-hydroxylase/17,20-liase) insufficiency

Deficiency of Р450с17 (17a-hydroxylase/17,20-liase) is а rare hereditary steroidogenesis defects disordering the synthesis of sex steroids and leading to excessive production of mineralocorticoid production. Clinical findings and results of molecular and hormonal studies in 6patients with P450cl7 deficiency are presented. All patients were born with female phenotype, 5 with male karyotype and 1 with female karyotype. Testicular feminization was erroneously diagnosed in all genetic men, and the genetic woman was treated for ovarian in sufficiency. Five of 6 patients suffered from severe arterial hypertension (up to 100/130 mm Hg). Hypopotassemia was observed in 3 patients. P450cl7 deficiency was diagnosed on the basis of increased serum corticosterone level, and in 4 patients it was confirmed by multisteroid analysis. Amplification and subsequent direct sequencing of CYP17gene revealed homozygotic mutation in exon 1 (R96Q) in 1 patient. The same mutations in exon 6 (V360L) were detected in 2 unrelated families (4 patients). Constituent heterozygosis by 2 mutations, in exon 6 (R347C) and exon 8 (R416C), was detected in 1 patient. These findings evidence the need in differential diagnosis of P450cl7 deficiency and the testicular feminization syndrome.

1. Тюльпаков А. Н., Калинченко С. Ю., Рожинская Л. Я. и др. // Пробл. эндокринол. - 1998. - № 6. - С. 39-43.

2. Biason-Laiiber A., Leibermcin Е., Zachmann М. // J. Clin. En docrinol. Metab. - 1997. - Vol. 82. - P. 3807-3812.

3. Biglieri E. G., Herron M. A., Brust N. // J. Clin. Invest. - 1966. - Vol. 45, N 12. - P. 1946-1954.

4. Geller D. H., Auchus R. J., Mendonca В. B., Miller W. L. // Nature Genet. - 1997. - Vol. 17. - P. 201-205.

5. New M. I. /1 J. Clin. Invest. - 1970. - Vol. 49, N 10. - P. 1930-1941.

6. Piccido-Leonard J., Miller W. L. // DNA. - 1987. - Vol. 6.- p. 439-448.

7. Sippell W. G., Bidlingmaier F., Becker H. et al. // J. Steroid Biochem. - 1978. - Vol. 9. - P. 63-74.

8. Sparkes R. S., Klisak I., Miller W. L. // DNA Cell Biol. - 1991. - Vol. 10. - P. 359-365.

9. Yanase T., Simpson E. R., Waterman M. R. // Endocr. Rev. - 1991. - Vol. 12. - P. 91-108.