References

nid

Нефрология и диализ

Nephrology and Dialysis

1680-44222618-9801

Российское диализное общество

10.28996/2618-9801-2020-3-293-311

nid-213

Research Article

ОБЗОРЫ И ЛЕКЦИИ

REVIEWS AND LECTURES

Клиническая интеграция генетической диагностики в педиатрическую нефрологию. Обзор литературы

Clinical integration of genetic diagnostics to pediatric nephrology. Review

Приходина

Л. С.

Prikhodina

L. S.

prikhodina@rambler.ru

ФГАОУ ВО «Российский Национальный Исследовательский Медицинский Университет им. Н.И. Пирогова» Министерства Здравоохранения Российской Федерации; ФГБОУ ДПО «Российская Медицинская Академия Непрерывного Профессионального Образования» Министерства Здравоохранения Российской ФедерацииРоссияPirogov Russian National Research Medical University; Russian Academy of Medical Continuous Postgraduate EducationRussian Federation

2020

29072024

223293311

2024

Приходина Л.С.

Prikhodina L.S.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://journal.nephro.ru/jour/article/view/213

Наследственные заболевания почек являются одной из ведущих причин хронической болезни почек в детском возрасте. Диагностика генетически-ассоциированных заболеваний почек на клиническом уровне нередко сложна вследствие выраженной генетической гетерогенности патологии и клинического полиморфизма проявлений. В последние годы в клинической практике применяется массовое параллельное секвенирование, разновидностью которого являются методы секвенирования нового поколения. Современное генетическое тестирование привело к улучшению диагностики генетически гетерогенных заболеваний, идентификации новых генов, что способствовало значительному прогрессу в понимании патогенетических механизмов, выявлению ранее нераспознанных фенотипов, а также реклассификации ряда заболеваний почек, включая COL4A-ассоциированную гломерулопатию и аутосомно-доминантные тубуло-интерстициальные заболевания почек. В обзоре представлены различные типы наследования моногенных заболеваний на примере патологии почек, сгруппированные из медицинской базы данных OMIM. Приводятся литературные сведения о современных молекулярно-генетических и цитогенетических методах диагностики, включая секвенирование по Сэнгеру, таргетные мультигенные панели, технологии массового параллельного секвенирования экзома и генома, а также хромосомный микроматричный анализ. Освещены в сравнительном аспекте преимущества и ограничения молекулярно-генетических методов диагностики. Представлены показания к генетическому обследованию при подозрении на наследственный характер патологии почек, обращается внимание на необходимость интерпретации данных генетических исследований в соответствие с международными и российскими рекомендациями профессиональных сообществ медицинских генетиков. В статье приводится алгоритм генетической диагностики с примерами клинического применения в нефрологической практике, включая обоснованные диагностические и терапевтические подходы. Представлены клинические ситуации, при которых проведение генетического тестирования может позволить пациентам избежать избежать нефробиопсии или иммуносупрессивной терапии с потенциальными побочными эффектами. Показано, что применение генетических методов исследования в педиатрической нефрологии является необходимым диагностическим инструментом для поиска причин наследственных заболеваний, выбора фармакотерапии, прогнозирования течения заболевания, а также медико-генетического консультирования семей пациентов и пренатальной диагностики наследственных заболеваний.

Hereditary kidney disease is a major cause of chronic kidney disease in childhood. Diagnosis of inherited kidney diseases in clinics is often complicated by the genetic heterogeneity of the pathology and clinical polymorphism of manifestations. Mass parallel sequencing with modern sequencing methods has been used in clinical practice over recent years. Up-to-date genetic testing has improved the diagnosis of various inherited diseases, which contributed to significant progress in the understanding of pathogenetic mechanisms, the identification of previously unrecognized phenotypes, and the reclassification of a number of kidney diseases, including COL4A-associated glomerulopathy and autosomal dominant tubulointerstitial diseases. The review presents various types of inheritance of monogenic diseases using the example of kidney pathology, grouped according to the OMIM medical database. The literature provides information concerning the up-to-date inherited of genetic and cytogenetic diagnostic, including Sanger sequencing, targeted multigene panels, technologies for massively parallel sequencing of the exome and genome, as well as chromosomal microarray analysis. The advantages and limitations of the molecular genetic diagnostic methods are highlighted in a comparative aspect. The indications for genetic testing in the case of suspicion of a hereditary nature of kidney pathology are presented, attention is drawn to the need to interpret the data of genetic studies in accordance with international and Russian national recommendations of professional communities of medical geneticists. The review an algorithm for genetic diagnostics with examples of clinical application in nephrological practice, including reasonable diagnostic and therapeutic approaches. Clinical situations in which genetic testing may allow patients to avoid kidney biopsy or immunosuppressive therapy with potential side effects are presented. It is shown that the use of genetic methods in pediatric nephrology is a necessary diagnostic tool for finding the causes of hereditary diseases, choosing pharmacotherapy, predicting the course of the disease, as well as medical and genetic counseling of patients' families and prenatal diagnosis of hereditary diseases.

педиатрическая нефрологиягенетикадетинаследственные заболевания почексеквенирование нового поколениягеныpediatric nephrologygeneticschildrenhereditary kidney diseasesnext-generation sequencinggenes

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