problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13544problendo-13544Research ArticleДетская эндокринологияPediatric EndocrinologyКлиническая, гормональная и молекулярно-генетическая характеристики 18 случаев нарушения формирования пола (НФП) 46XY, ассоциированных с вариантами в гене SRD5A2Clinical, hormonal and molecular genetic characteristics of 18 cases of disorders of sex development (DSD) 46,XY associated with variants in the SRD5A2 genehttps://orcid.org/0000-0002-2000-7694КалинченкоН. Ю.KalinchenkoN. Y.

Калинченко Наталья Юрьевна, к.м.н. 

117036, Москва, ул. Дм. Ульянова, д. 11

Natalia Y. Kalinchenko, MD, PhD

11 Dm. Ulyanova street, 117036 Moscow

kalinnat@rambler.ruhttps://orcid.org/0000-0003-0412-7140МакрецкаяН. А.MakretskayaN. A.

Макрецкая Нина Алексеевна, к.м.н. 

Москва

Nina A. Makretskaya, MD, PhD

Moscow

makretskayan@gmail.comhttps://orcid.org/0000-0001-7736-5372КолодкинаА. А.KolodkinaA. A.

Колодкина Анна Александровна, к.м.н. 

Москва

Anna A. Kolodkina, MD, PhD

MoscowI_marusya@mail.ru

anna_kolodkina@mail.ruhttps://orcid.org/0000-0003-1320-6561КареваМ. А.KarevaM. A.

Карева Мария Андреевна, д.м.н. 

Maria A. Kareva, PhD

I_marusya@mail.ruhttps://orcid.org/0000-0001-8500-4841ТюльпаковА. Н.TiulpakovA. N.

Тюльпаков Анатолий Николаевич, д.м.н. 

Москва

Anatoliy N. Tyulpakov, MD, PhD

Moscow

anatolytiulpakov@gmail.comНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CenterRussian FederationМедико-генетический научный центр имени академика Н.П. БочковаРоссияResearch Centre for Medical GeneticsRussian Federation2025021220257154046Copyright © Калинченко Н.Ю., Макрецкая Н.А., Колодкина А.А., Карева М.А., Тюльпаков А.Н., 20252025Калинченко Н.Ю., Макрецкая Н.А., Колодкина А.А., Карева М.А., Тюльпаков А.Н.Kalinchenko N.Y., Makretskaya N.A., Kolodkina A.A., Kareva M.A., Tiulpakov A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/13544АКТУАЛЬНОСТЬ

АКТУАЛЬНОСТЬ. В структуре нарушений формирования пола (НФП) при кариотипе 46,XY выделяют группу нозологий, обусловленных нарушением синтеза андрогенов, последним этапом которого является превращение тестостерона в более активный андроген дигидротестостерон, что происходит под влиянием фермента 5α-редуктазы II типа (SRD5A2). Дефицит SRD5A2 является редким заболеванием с аутосомно-рецессивным наследованием.

ЦЕЛЬ

ЦЕЛЬ. Дать клиническую и молекулярно-генетическую характеристику 14 новых случаев с подтвержденным молекулярно-генетическим методом дефицитом SRD5A2, а также 4 случаев НФП 46,XY, где были выявлены моноаллельные изменения в гене SRD5A2.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. В исследование было включено 310 пациентов с НФП 46,XY. Молекулярно-генетический анализ проводился методом NGS с использованием таргетной панели для мультиплексной амплификации и последующего секвенирования кодирующих последовательностей следующих генов: AKR1C2, AKR1C4, AMH, AMHR2, AR, ARX, ATRX, CBX2, CYB5A, CYP11A1, CYP17A1, DHCR7, DHH, EMX2, ESR2, FGD1, FGF9, FGFR2, FKBP4, FOXF2, FOXL2, HOXA13, HSD17B3, HSD3B2, ICK, LHCGR, LHX1, LHX9, MAMLD1, MAP3K1, MID1, NR0B1, NR5A1, POR, PTGDS, SOX9, SRD5A2, SRY, STAR, SUPT3H, TSPYL1, WNT4, WT1, ZFPM2.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. При молекулярно-генетическом обследовании в гене SRD5A2 было идентифицировано 16 различных вариантов (2 — в нескольких семьях), 4 из которых ранее описаны не были.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Проведенное исследование подчеркивает важное значение молекулярно-генетического анализа в дифференциальной диагностике НФП 46,XY.

INTRODUCTION

INTRODUCTION. Among the disorders of sex development (DSD) with karyotype 46,XY, there is a group of diseases caused by defects of androgen synthesis. The last stage of in the synthesis of androgens is the conversion of testosterone into a more active androgen dihydrotestosterone, which occurs under the influence of the enzyme 5α-reductase type II (SRD5A2). SRD5A2 deficiency is a rare disease with autosomal recessive inheritance.

AIM

AIM. To give a clinical and molecular genetic characterization of 14 new cases with confirmed molecular diagnosis of SRD5A2 deficiency, as well as 4 cases of DSD 46,XY, where monoallelic changes in the SRD5A2 gene were detected.

MATERIALS AND METHODS

MATERIALS AND METHODS. The study included 310 patients with DSD 46,XY. Molecular genetic analysis was performed using the NGS method using a targeted panel for multiplex amplification and subsequent sequencing of the coding regions of the following genes: AKR1C2, AKR1C4, AMH, AMHR2, AR, ARX, ATRX, CBX2, CYB5A, CYP11A1, CYP17A1, DHCR7, DHH, EMX2, ESR2, FGD1, FGF9, FGFR2, FKBP4, FOXF2, FOXL2, HOXA13, HSD17B3, HSD3B2, ICK, LHCGR, LHX1, LHX9, MAMLD1, MAP3K1, MID1, NR0B1, NR5A1, POR, PTGDS, SOX9, SRD5A2, SRY, STAR, SUPT3H, TSPYL1, WNT4, WT1, ZFPM2.

RESULTS

RESULTS. By molecular genetic analysis 16 different variants were identified in the SRD5A2 gene (2 in several families), 4 of which had not been previously described.

CONCLUSION

CONCLUSION. The study highlights the importance of molecular genetic analysis in the differential diagnosis of DSD 46,XY.

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The authors declare that there are no conflicts of interest present.