vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.403vavilov-1598Research ArticleГЕНЕТИКА ЧЕЛОВЕКАHUMAN GENETICSПолноэкзомный анализ первичного иммунодефицитаWhole exome analysis of primary immunodeficiencyРахманиЭ. Ш.RahmaniE. S.

Факультет медицинских биотехнологий, Школа комплементарной медицины

Тегеран

Department of Medical Biotechnology, College of Allied Medicine

Tehran

АзарпараХ.AzarparaН.

Факультет медицины

Тегеран

Department of Medicine

Tehran

КаримипурM.KarimipoorM.

Факультет молекулярной медицины

Тегеран

Department of Molecular Medicine

Tehran

РахимиХ.RahimiН.

Факультет молекулярной медицины

Тегеран

Department of Molecular Medicine

Tehran

rahimi.h1981@gmail.comИранский университет медицинских наукИранIran University of Medical SciencesIslamic Republic of IranИсследовательский центр биотехнологий, Институт Пастера ИранаИранBiotechnology Research Center, Pasteur Institute of IranIslamic Republic of Iran201809082018225620626Copyright © Рахмани Э.Ш., Азарпара Х., Каримипур M., Рахими Х., 20182018Рахмани Э.Ш., Азарпара Х., Каримипур M., Рахими Х.Rahmani E.S., Azarpara Н., Karimipoor M., Rahimi Н.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1598

Первичный иммунодефицит представляет собой гетеро­генную группу редких наследственных мутаций единич­ного гена, вызывающих сбой в работе иммунной системы человека и проявляющихся в предрасположенности пациентов к тяжелым жизнеугрожающим инфекциям. Гетеро­генная природа первичного иммунодефицита, при которой мутации могут быть подвержены по меньшей мере 300 различных генов, серьезно осложняет его диагностику. И хотя было подсчитано, что от этого заболевания могут страдать около шести миллионов человек, только немно­гие из них могут рассчитывать на постановку правильного диагноза. Однако развитие методов секвенирования ДНК и доступность высокотехнологичного оборудования позволили сделать значительный шаг вперед в области моле-кулярных исследований генетических заболеваний. Тех­нология полноэкзомного анализа ДНК может оказать существенную помощь врачам при диагностировании менде­левских предрасположенностей к микробактериальным инфекциям и других форм редких генетических заболеваний. В представленном исследовании мы использовали метод полноэкзомного анализа ДНК для обследования двух младенцев с симптомами первичного иммунодефи­цита, такими как гемофагоцитарный лимфогистиоцитоз (ГЛГ) и тяжелый комбинированный иммунодефицит (ТКИД). Полноэкзомный анализ выявил мутацию UNC13D гена (NM_199242.2:c.627delT) у пациента с ГЛГ и мутацию RAG1 гена (NM_000448.2:c.322C>G) – у пациента с ТКИД. Исследо­вание показало, что полноэкзомный анализ – это быстрый и экономичный метод, помогающий поставить правильный диагноз пациентам с первичным иммунодефицитом.

The human primary immunodeficiency diseases (PIDs) refer to a rare heterogeneous group of single-gene inherited disorders causing malfunctions in the immune system, and thus the affected patients have a predisposition to severe life-threatening infections. The heterogeneous nature of PIDs, which involves at list 300 different genes, makes diagnosis of the disease a complex issue. Although studies revealed that six million people have a kind of PID, but due to a complex diagnosis procedure many affected individuals have not gotten a correct diagnosis. However, thanks to advancing in the DNA sequencing method and availability of sophisticated sequencers molecular characterization of genetic disorders have been revolutionized. The whole exome sequencing (WES) method can help clinicians detect Mendelian disease and other complex genetic disorders. The presented study used WES to investigate two infants with symptoms of primary immunodeficiency including hemophagocytic lymphohistio­cytosis (HLH) and severe combined immunodeficiency (SCID). It has been shown that the HLH patient had a mutation in the UNC13D gene (NM_199242.2:c.627delT), and the SCID patient had a mutation in the RAG1 gene (NM_000448.2:c.322C>G). It has been demonstrated that WES is a fast and cost-effective method facilitating genetic diagnosis in PID sufferers.

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