problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl13436problendo-13436Research ArticleДетская эндокринологияPediatric EndocrinologyСлучай тестикулярного нарушения формирования пола при кариотипе 46,XX, обусловленный мнимым синонимичным вариантом в гене WT1: трудности дифференциальной диагностики синдрома внутриутробной вирилизации у девочкиA case of 46,XX testicular disorders of sex development due to an apparent synonymous variant in the WT1 gene: difficulties of differential diagnosis of intrauterine virililzation syndrome in a girlhttps://orcid.org/0000-0001-7894-9222БуяноваА. А.BuianovaA. A.

Буянова Анастасия Александровна

Москва

Anastasiia A. Buianova

Moscow

anastasiiabuianova97@gmail.comВоронцоваИ. Г.VorontsovaI. G.

Воронцова Инна Геннадьевна

Москва

Inna G. Vorontsova

Moscow

vorontsova-inna@mail.ruhttps://orcid.org/0009-0001-8941-7034СамитоваА. Ф.SamitovaA. F.

Самитова Алина Фаритовна

Москва

Alina F. Samitova

Moscow

alinasamitova16@gmail.comhttps://orcid.org/0000-0003-2863-1659ВасилиадисЮ. А.VasiliadisYu. A.

Василиадис Юлия Андреевна

Москва

Iuliia A. Vasiliadis

Moscow

julia.vasiliadis@gmail.comhttps://orcid.org/0000-0002-8520-2378ПетряйкинаЕ. Е.PetryaykinaE. E.

Петряйкина Елена Ефимовна, д.м.н. 

119571, Москва, Ленинский пр-т, д. 117, корп. 1 

Elena E. Petryaykina, MD, PhD

117 bldg. 1 Leninsky Prospekt, 119571 Moscow

lepet_morozko@mail.ruДеминаЕ. С.DeminaE. S.

Демина Елена Степановна

Москва

Elena S. Demina

Moscow

demina_elena72@mail.ruhttps://orcid.org/0000-0001-8500-4841ТюльпаковА. Н.TyulpakovA. N.

Тюльпаков Анатолий Николаевич, д.м.н.

Москва

Anatoliy N. Tyulpakov, MD, PhD

Moscow

anatolytiulpakov@gmail.comЦентр высокоточного редактирования и генетических технологий для биомедициныРоссияCenter for High-Precision Editing and Genetic Technologies for BiomedicineRussian FederationРоссийская детская клиническая больницаРоссияRussian Children’s Clinical HospitalRussian FederationРоссийская детская клиническая больница; Медико-генетический научный центр им. акад. Н.П. БочковаРоссияRussian Children’s Clinical Hospital; Medical Genetic Research Center named after Academician N.P. BochkovRussian Federation2025020420247116065Copyright © Буянова А.А., Воронцова И.Г., Самитова А.Ф., Василиадис Ю.А., Петряйкина Е.Е., Демина Е.С., Тюльпаков А.Н., 20252025Буянова А.А., Воронцова И.Г., Самитова А.Ф., Василиадис Ю.А., Петряйкина Е.Е., Демина Е.С., Тюльпаков А.Н.Buianova A.A., Vorontsova I.G., Samitova A.F., Vasiliadis Y.A., Petryaykina E.E., Demina E.S., 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/13436

Термин нарушения формирования пола (НФП) объединяет группу врожденных состояний, при которых имеет место несоответствие между хромосомным и (или) гонадным полом и строением половых органов. К одной из групп НФП относятся тестикулярные нарушения при кариотипе 46,XX (ТНФП_46,XX), в структуре которой выделяют формы, обусловленные транслокацией гена SRY, и более редко — SRY-негативные формы. В настоящем сообщении нами представлено наблюдение пациента с SRY-негативным ТНФП_46,XX, у которого первоначально состояние расценивалось как вирильная форма врожденной дисфункции коры надпочечников (ВДКН), затем — как идиопатическая внутриутробная вирилизация у девочки. На фоне вирилизации в возрасте 11 лет было заподозрено наличие тестикулярной ткани. При молекулярно-генетическом обследовании (полноэкзомное секвенирование с валидацией методом С энгера) был обнаружен de novo вариант в экзоне 9 гена WT1 (chr11:32413528T>C), который по предсказаниям не приводил к изменению аминокислотной последовательности (p.Thr479=, NM_024426.6), однако нарушал сплайсинг, результатом чего было характерное для ТНФП_46,XX изменение C-концевого домена WT1. После верификации диагноза проведена гонадэктомия и назначена заместительная терапия эстрогенами. Таким образом, нами описан пациент с редкой формой ТНФП_46,XX, обусловленного вариантом в гене WT1. Представленное наблюдение иллюстрирует сложности дифференциальной диагностики синдрома внутриутробной вирилизации при женском кариотипе.

Disorders of sex development (DSD) represent a group of congenital conditions in which there is a discrepancy between the chromosomal and (or) gonadal sex and the structure of the genitals. Within the DSD there is a subgroup of 46,XX testicular DSD (46,XX TDSD), which may be caused by the translocation of the SRY gene, and more rarely — due to other causes (SRY-negative forms). In this report, we present an observation of a patient with SRY-negative 46,XX TDSD, in whom the condition was initially regarded as a virile form of congenital adrenal hyperplasia, then as idiopathic intrauterine virilization in a girl. Due to the development of virilization at the age of 11, the presence of testicular tissue was suspected. Molecular genetic analysis (whole exome sequencing with Sanger validation) revealed a de novo variant in exon 9 of the WT1 gene (chr11:32413528T>C), which, according to predictions, did not lead to a change in the amino acid sequence (p.Thr479=, NM_024426.6), but disrupted splicing, resulting in a previously described in 46,XX TDSD a change in the C-terminal domain of WT1. After verification of the diagnosis, a gonadectomy was performed and estrogen replacement therapy was prescribed. Thus, we have described a patient with a rare form of 46,XX TDSD caused by a variant in the WT1 gene. The presented observation illustrates the difficulties of differential diagnosis of intrauterine virilization syndrome in female karyotype.

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