Клиническая, гормональная и молекулярно-генетическая характеристика трех случаев нарушения формирования пола 46XY, обусловленного дефицитом 5α-редуктазы II типа

Дефицит 5α-редуктазы II типа (5-АРII) - одна из причин нарушения формирования пола у мальчиков. Наиболее важно провести дифференциальную диагностику с неполной формой синдрома нечувствительности к андрогенам, при которой из-за неэффективности терапии андрогенами адаптация в мужском поле крайне нежелательна, тогда как при дефиците 5-АРII адаптация в мужском поле социально оправдана, а в некоторых случаях позволяет сохранить фертильность. Представленные нами случаи демонстрируют невысокую диагностическую значимость определения соотношения Т/ДГТ (по крайней мере, при определении последнего иммуноферментным методом) и подчеркивают необходимость анализа гена SRD5A2 у всех пациентов с подозрением на дефицит 5-АРII.

нарушение формирования пола, дефицит 5α-редуктазы II типа, ген SRD5A2

1. MacLaughlin D.T., Donahoe P.K. Sex determination and differentiation. N Engl J Med 2004;350:367-378.

2. Katz M.D., Cai L.-Q., Zhu Y.S. et al. The biochemical and phenotypic characterization of females homozygous for 5α-reductase 2 deficiency. J Clin Endocrinol Metab 1995;80:3160-3167.

3. Zhu Y.S., Imperato-McGinley J. Male pseudohermaphroditism due to 5alpha-reductase-2 deficiency. In: Gynecology and Obstetrics. Ed. J.J. Sciarra. Lippincoft Williams & Wilkins 2002.

4. Hochberg Z., Chayen R., Falik Z. et al. Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5α-reductase 2 deficiency. J Clin Endocrinol Metab 1996;81:2821-2827.

5. Wilson J.D., Griffin J.E., Russel D.W. Steroid 5α-reductase 2 deficiency.Endocr Rev 1993;14:577-593.

6. Den Dunnen J.T., Antonarakis S.E. Nomenclature for the description of human sequence variations. Hum Genet 2001;109:1:121-124.

7. De Vaal O.M. Genital intersexuality in three brothers, connected with consanguineous marriages in the three previous generations. Acta Paediat 1955;44:35-39.

8. Wilson J.D., Goldstein J.L. Classification of hereditary disorders of sexual development. Birth Defects Orig Artic Ser 1975;11:4:1-16.

9. Wilson J.D. Metabolism of testicular androgens. In: Handbook of Physiology. Eds. R.O. Greep, E.B. Astwood. vol 5: Endocrinology, sec 7: Male Reproductive System. Am Physiol Soc (Washington) 1975;491-508.

10. Goro Sasaki, Tsutomu Ogata, Tomohiro Ishii et al. Micropenis and the 5-Reductase-2 (SRD5A2) Gene:Mutation and V89L Polymorphism Analysis in 81 Japanese Patients. J Clin Endocrinol Metabol 2003;88:7:3431-3436.

11. Imperato-McGinley J., Zhu Y.S. Androgens and male physiology the syndrome of 5α-reductase-2 deficiency. Mol Cel Endocrinol 2002;198:51-59.

12. Katz M.D., Kligman I., Cai L.-Q. et al. Paternity in intrauterine insemination with sperm from a man with 5-alpha-reductase-2 deficiency. New Eng J Med 1997;336:994-997.

13. Walsh P.C., Madden J.D., Harrod M.J. et al. Familial incomplete male pseudohermaphroditism type 2: Decreased dihydrotestosterone formation in pseudovaginal perineo-scrotal hypospadias. New Engl J Med 1974;291:944.

14. Wilson J.D. Dihydrotestosterone formation in cultured human fibroblasts: Comparison of cells from normal subjects and patients with familial incomplete male pseudohermaphroditism, type 2. J Biol Chem 1975;250:3498.

15. Peterson R.E., Imperato-McGinley J., Gautier T., Sturla E. Male pseudohermaphroditism due to steroid 5α-reductase deficiency. Am J Med 1977;62:170.

16. Imperato-McGinley J., Gautier T., Pichardo M., Shackleton C. The diagnosis of 5α-reductase deficiency in infancy. J Clin Endocrinol Metab 1986;63:1313.

17. Mendonca B.B., Inacio M., Costa E.M.F. et al. Male pseudohermaphroditism due to steroid 5α-reductase 2 deficiency: Diagnosis, psychological evaluation, and management. Medicine 1996;75:64.

18. Ogilvy-Stuart A.L., Brain C.E. Early assessment of ambiguous genitalia. Arch Dis Child 2004;89:401-407.

19. Andersson S., Russell D.W. Structural and biochemical properties of cloned and expressed human and rat steroid 5α-reductases. Proc Natl Acad Sci 1990;87:3640-3644.

20. Andersson S., Berman D.M., Jenkins E.P. et al. Deletion of steroid 5α-reductase-2 gene in male pseudohermaphroditism. Nature 1991;354:159-161.

21. Thigpen A.E., Silver R.I., Guileyardo J.M. et al. Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression. J Clin Inv 1993;92:2:903-910.doi: 10.1172/JCI116665.

22. Imperato-McGinley J., Miller M., Wilson J. D. et al. A cluster of male pseudohermaphrodites with 5-alpha-reductase deficiency in Papua New Guinea. Clin Endocr 1991;34:293-298.

23. Nordenskjold A., Ivarsson S.-A. Molecular characterization of 5-alpha-reductase type 2 deficiency and fertility in a Swedish family. J Clin Endocr Metab 1998;83:3236-3238.