problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13415problendo-13415Research ArticleДетская эндокринологияPediatric EndocrinologyКлиническая, гормональная и молекулярно-генетическая характеристика случаев нарушения формирования пола при кариотипе 46,XY, ассоциированных с вариантами в гене HSD17B3Clinical, hormonal and molecular genetic characteristics of patients with 46,XY disorders of sex development associated with variants in the HSD17B3 genehttps://orcid.org/0000-0002-2000-7694КалинченкоН. Ю.KalinchenkoN. Y.

Калинченко Наталья Юрьевна, к.м.н.

Москва

Nataliya Y. Kalinchenko, MD, PhD

Moscow

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

Макрецкая Нина Алексеевна, к.м.н.

ул. Москворечье, д. 1, 115522, Москва

Nina A. Makretskaya, MD, PhD

1 Moskvorechye street, 115522 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, senior research associate

Moscow

anna_kolodkina@mail.ruhttps://orcid.org/0000-0001-9002-1662ИоутсиВ. А.IoutsiV. A.

Иоутси Виталий Алексеевич, к.х.н.

Москва

Vitaliy A. Ioutsi, PhD

Moscow

vitalik_org@mail.ruhttps://orcid.org/0000-0002-0520-9132ПетровВ. М.PetrovV. M.

Петров Василий Михайлович, к.х.н., с.н.с.

Москва

Vasily M. Petrov, PhD, senior research associate

Moscow

petrov.vasiliy@gmail.comhttps://orcid.org/0000-0001-8500-4841ТюльпаковА. Н.TyulpakovA. N.

Тюльпаков Анатолий Николаевич, д.м.н.

Москва

Anatoliy N. Tyulpakov, MD, PhD

Moscow

anatolytiulpakov@gmail.comНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian FederationМедико-генетический научный центр имени академика Н.П. БочковаРоссияResearch Centre for Medical GeneticsRussian FederationМедико-генетический научный центр имени академика Н.П. Бочкова; Российская детская клиническая больницаРоссияResearch Centre for Medical Genetics; Russian Children’s Clinical HospitalRussian Federation2024090120247069198Copyright © Калинченко Н.Ю., Макрецкая Н.А., Колодкина А.А., Иоутси В.А., Петров В.М., Тюльпаков А.Н., 20252025Калинченко Н.Ю., Макрецкая Н.А., Колодкина А.А., Иоутси В.А., Петров В.М., Тюльпаков А.Н.Kalinchenko N.Y., Makretskaya N.A., Kolodkina A.A., Ioutsi V.A., Petrov V.M., Tyulpakov 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/13415

ОБОСНОВАНИЕ. Недостаточность 17β-гидроксистероиддегидрогеназы типа 3 (HSD17B3) является редким вариантом нарушения формирования пола (НФП) при кариотипе 46,XY. В настоящее время в отечественной литературе отсутствуют обобщенные данные по указанной группе пациентов, что затрудняет проведение своевременной диагностики и выбор тактики лечения.ЦЕЛЬ. Дать клиническую, гормональную и молекулярно-генетическую характеристику случаев НФП 46,XY, ассоциированных с вариантами в гене HSD17B3.МАТЕРИАЛЫ И МЕТОДЫ. Одноцентровое ретроспективное исследование, включившее 310 пациентов с НФП 46,XY. Пациентам проводилось комплексное обследование, включающее исследование стероидного профиля методом высокоэффективной жидкостной хроматографии с тандемным масс-спектрометрическим детектированием, а также молекулярно-генетическое исследование с использованием NGS.РЕЗУЛЬТАТЫ. По результатам проведенных молекулярно-генетических исследований биаллельные нуклеотидные замены в гене HSD17B3 выявлены в 13 случаях, что составило 4,2% от общего числа пациентов с НФП 46,XY. Все 13 пациентов с биаллельными вариантами в гене HSD17B3 зарегистрированы в женском поле. Соотношение концентраций андростендиона/тестостерона в крови в этой группе варьировало от 1,4 до 8,9. Два варианта в гене HSD17B3 встречались у нескольких пациентов: c.277+4A>T (на 6 хромосомах) и c.729_735del:p.V243fs (на 9 хромосомах). Выявлено 4 ранее не описанных варианта. Моноаллельные нуклеотидные замены в гене HSD17B3 выявлены в 7 случаях, что составило 2,3% от общего числа пациентов с НФП 46,XY. Строение наружных гениталий в данной группе соответствовало стадиям 3–4 по Прадеру. У 1 пациента в гене HSD17B3 выявлен патогенный вариант c.277+4A>T, в остальных случаях определялись варианты с неопределенным клиническим значением.ЗАКЛЮЧЕНИЕ. В структуре НФП 46,XY пациенты с биаллельными вариантами в гене HSD17B3 выявлены в 4,2% случаев, с моноаллельными вариантами — в 2,3% случаев. Обнаружены 4 ранее не описанные варианта в гене HSD17B3.

BACKGROUND: Deficiency of 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is a rare variant of 46,XY disorders of sex development (DSD).AIM: To give clinical, hormonal and molecular genetic characteristics of cases of 46,XY DSD associated with variants in the HSD17B3 gene.MATERIALS AND METHODS: The study included 310 patients with 46,XY DSD for the period from 2015 to 2019. The patients underwent a comprehensive examination, including a study of the steroid profile by high-performance liquid chromatography with tandem mass spectrometric detection, as well as a molecular genetic analysis using NGS.RESULTS: According to the results of molecular genetic studies, biallelic nucleotide substitutions in the HSD17B3 gene were detected in 13 cases, which accounted for 4.2% of the total number of patients with 46,XY DSD. All 13 patients with biallelic variants in the HSD17B3 gene were registered as females. The ratio of androstenedione/testosterone concentrations in the blood in this group ranged from 1.4 to 8.9. 2 variants in the HSD17B3 gene were found in several patients: c.277+4A>T (on 6 chromosomes) and c.729_735del:p.V243fs (on 9 chromosomes). 4 novel variants have been identified. Monoallelic nucleotide substitutions in the HSD17B3 gene were detected in 7 cases, which accounted for 2.3% of the total number of patients with 46,XY DSD. External genitalia in this group corresponded to Prader stages 3–4. In 1 patient, a pathogenic variant c.277+4A>T was detected in the HSD17B3 gene, in other cases variants with uncertain significance were detected.CONCLUSION: In the structure of 46,XY DSD, patients with biallelic variants in the HSD17B3 gene were identified in 4.2% of cases, with monoallelic variants — in 2.3% of cases. 4 novel variants were found in the HSD17B3 gene.

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