medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.07.24-32medgen-2506Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHСпектр патогенных вариантов генов потенциальных мишеней таргетной терапии при PROS (спектр синдромов избыточного роста, ассоциированных с мутацией в гене PIK3CA)Potentially actionable pathogenic genetic variants in PROS (PIK3CA-related overgrowth spectrum)БычковаЕ. В.BychkovaE. V.

Бычкова Екатерина Владимировна

115522, г. Москва, ул. Москворечье, д.1

Ekaterina V. Bychkova

1 Moskvorechie st., Moscow, 115522

ktrn.bychkova@gmail.comСеменоваН. А.SemenovaN. A.

115522, г. Москва, ул. Москворечье, д.1

1 Moskvorechie st., Moscow, 115522

СагоянГ. Б.SagoyanG. B.

115522, г. Москва, Каширское шоссе, д. 23

23 Kashirskoe shosse, Moscow, 115522

ХагуровР. А.KhagurovR. A.

123242, г. Москва, ул. Садово-Кудринская, д. 15

15 Sadovaya-Kudrinskaya sSt., Moscow, 123242

ГусеваД. М.GusevaD. M.

115522, г. Москва, ул. Москворечье, д.1

1 Moskvorechie st., Moscow, 115522

ВолодинИ. В.VolodinI. V.

115522, г. Москва, ул. Москворечье, д.1

1 Moskvorechie st., Moscow, 115522

СмирновА. С.SmirnovA. S.

115522, г. Москва, ул. Москворечье, д.1

117513, г. Москва, ул. Островитянова, д. 1

1 Moskvorechie st., Moscow, 115522

1 Ostrovityanova st., Moscow, 117513

СтрельниковВ. В.StrelnikovV. V.

115522, г. Москва, ул. Москворечье, д.1

1 Moskvorechie st., Moscow, 115522

ФГБНУ Медико-генетический научный центр имени академика Н.П. БочковаРоссияResearch Centre for Medical GeneticsRussian FederationФГБУ Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина Министерства здравоохранения Российской ФедерацииРоссияNational Medical Research Center of Oncology named after N.N. Blokhin of the Ministry of Health of the Russian FederationRussian FederationГБУЗ города Москвы Детская городская клиническая больница им. Н.Ф. Филатова Департамента здравоохранения города МосквыРоссияChildren’s City Clinical Hospital named after N.F. Filatov of Moscow City Health DepartmentRussian FederationФГБНУ Медико-генетический научный центр имени академика Н.П. Бочкова; ФГАОУ ВО Российский национальный исследовательский медицинский университет имени Н.И. Пирогова Министерства здравоохранения Российской ФедерацииРоссияResearch Centre for Medical Genetics; N.I. Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian FederationRussian Federation2024101020242372432Copyright © Бычкова Е.В., Семенова Н.А., Сагоян Г.Б., Хагуров Р.А., Гусева Д.М., Володин И.В., Смирнов А.С., Стрельников В.В., 20242024Бычкова Е.В., Семенова Н.А., Сагоян Г.Б., Хагуров Р.А., Гусева Д.М., Володин И.В., Смирнов А.С., Стрельников В.В.Bychkova E.V., Semenova N.A., Sagoyan G.B., Khagurov R.A., Guseva D.M., Volodin I.V., Smirnov A.S., Strelnikov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2506

PROS (PIK3CA-related overgrowth spectrum − спектр синдромов избыточного роста, ассоциированных с мутацией гена PIK3CA) − гетерогенная группа заболеваний, характеризующихся разрастанием тканей, сосудистыми мальформациями и другими пороками развития. Причиной этих патологических состояний является соматическая активирующая мутация гена PIK3CA, возникающая в период эмбриогенеза. Широкое фенотипическое разнообразие заболевания создает трудности для клинической диагностики, поэтому молекулярно-генетическое тестирование имеет решающую роль в постановке диагноза и принятии решения о назначении ингибитора PI3Kα алпелисиба. В данной работе с использованием высокопроизводительного секвенирования панели генов-регуляторов клеточного роста у 29 из 80 пациентов с подозрением на PROS  были выявлены варианты в гене PIK3CA, у 1 пациента был обнаружен патогенный вариант в гене AKT1. Представлены клинические и молекулярно-генетические характеристики пациентов и обсуждены дальнейшие перспективы развития молекулярно-генетической диагностики PROS.  

PROS (PIK3CA-related overgrowth spectrum) is a heterogeneous group of diseases characterized by tissue overgrowth, vascular malformations, and other malformations. The cause of these pathologic conditions is a somatic activating PIK3CA mutation that occurs during embryogenesis. The wide phenotypic diversity of the disease complicates clinical diagnosis, so molecular genetic testing has a crucial role in the diagnosis and the decision to prescribe the PI3Kα inhibitor alpelisib. In this study, among 80 patients with suspected PROS, a variant in PIK3CA was identified in 29 patients using high-throughput sequencing of a panel of cell growth regulator genes, their clinical and molecular genetic characterization is presented, and further prospects for the development of molecular genetic diagnosis of PROS are discussed.

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