vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-46vavilov-3781Research ArticleГЕНЕТИКА ЧЕЛОВЕКАHUMAN GENETICSКлинико-генетические аспекты и молекулярный патогенез остеопетрозаClinical, genetic aspects and molecular pathogenesis of osteopetrosishttps://orcid.org/0000-0001-8981-688XНадыршинаД. Д.NadyrshinaD. D.

Уфа

Ufa

nadyrshinadina@gmail.comhttps://orcid.org/0000-0002-8643-850XХусаиноваР. И.KhusainovaR. I.

Уфа; Санкт-Петербург

Ufa; St. Petersburg

Уфимский университет науки и технологийРоссияUfa University of Science and TechnologyRussian FederationУфимский университет науки и технологий; Санкт-Петербургский государственный университетРоссияUfa University of Science and Technology; Saint Petersburg State UniversityRussian Federation202314072023274383392Copyright © Надыршина Д.Д., Хусаинова Р.И., 20232023Надыршина Д.Д., Хусаинова Р.И.Nadyrshina D.D., Khusainova R.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3781

Остеопетроз («мраморная кость», МКБ-10-78.2) включает группу наследственных нарушений костной системы, отличающихся клинической вариабельностью и генетической гетерогенностью. Название «остеопетроз» происходит от греческих слов: ỏστέον (остео) – кость, πέτρα (петросис) – камень, что характеризует основной признак заболевания – повышенную плотность костей, обусловленную нарушениями равновесия формирования и ремоделирования кости, приводящими к структурным изменениям в костной ткани, предрасположенности к переломам, деформациям скелета. Эти дефекты, в свою очередь, влияют на другие важные органы и ткани, особенно на костный мозг и нервную систему. Заболевание наследуется по аутосомно-рецессивному, аутосомно-доминантному типам, встречаются Х-сцепленные формы заболевания, а также спорадические случаи. Частота аутосомно-доминантного остеопетроза составляет 1 на 20 тыс., а аутосомно-рецессивного – 1 на 250 тыс. новорожденных. На сегодняшний день описано 23 гена, структурные изменения в которых приводят к развитию остеопетроза. Клинические симптомы при остеопетрозных состояниях сильно различаются по проявлению и степени тяжести. Наиболее легкие скелетные нарушения наблюдаются во взрослом возрасте и встречаются при аутосомно-доминантной форме остеопетроза. Тяжелые формы, характеризующиеся переломами, умственной отсталостью, поражениями кожи, нарушениями иммунной системы, ацидозом почечных канальцев, наблюдаются при аутосомно-рецессивном типе остеопетроза, проявляющемся в раннем детском возрасте. Диагноз «остеопетроз» ставится на основании клинической и рентгенологической оценки, подтвержденной биопсией костей и генетическим тестированием. Для аутосомно-рецессивных форм остеопетроза важны ранняя диагностика и лечение заболевания с целью установления гематологических нарушений, а также для предотвращения прогрессирования заболевания до возникновения необратимых неврологических последствий. Большинство пациентов умирают в течение первого десятилетия из-за вторичных инфекций и/или кровотечений, а также угнетения функции костного мозга. В настоящей работе представлен обзор современного состояния изучения остеопетроза, клинико-генетических аспектов, молекулярного патогенеза заболевания.

Osteopetrosis (“marble bone”, ICD-10-78.2) includes a group of hereditary bone disorders distinguished by clinical variability and genetic heterogeneity. The name “osteopetrosis” comes from the Greek language: ‘osteo’ means ‘bone’ and ‘petrosis’ means ‘stone’, which characterizes the main feature of the disease: increased bone density caused by imbalances in bone formation and remodeling, leading to structural changes in bone tissue, predisposition to fractures, skeletal deformities. These defects, in turn, affect other important organs and tissues, especially bone marrow and the nervous system. The disease can be autosomal recessive, autosomal dominant, X-linked or sporadic. Autosomal dominant osteopetrosis has an incidence of 1 in 20,000 newborns and autosomal recessive one has 1 in 250,000. To date, 23 genes have been described, structural changes in which lead to the development of osteopetrosis. Clinical symptoms in osteopetrosis vary greatly in their presentation and severity. The mildest skeletal abnormalities are observed in adulthood and occur in the autosomal dominant form of osteopetrosis. Severe forms, being autosomal recessive and manifesting in early childhood, are characterized by fractures, mental retardation, skin lesions, immune system disorders, renal tubular acidosis. Clinical examination and review of radiographs, bone biopsy and genetic testing provide the bases for clinical diagnosis. The early and accurate detection and treatment of the disease are important to prevent hematologic abnormalities and disease progression to irreversible neurologic consequences. Most patients die within the first decade due to secondary infections, bone marrow suppression and/or bleeding. This article summarizes the current state of the art in this field, including clinical and genetic aspects, and the molecular pathogenesis of the osteopetrosis.

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