Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66694810.31857/S0016675824040065creovsГЕНЕТИКА ЧЕЛОВЕКАResearch ArticleFrequent genetic variants of autosomal recessive non-syndromic forms of inherited retinal diseases in the Russian FederationЧастые генетические варианты аутосомно-рецессивных несиндромальных форм наследственных заболеваний сетчатки у жителей Российской ФедерацииOgorodovaN. Yu.ОгородоваН. Ю.
Russian Federation
ogorodova@med-gen.ruStepanovaA. A.СтепановаА. А.
Russian Federation
ogorodova@med-gen.ruShchaginaO. A.ЩагинаО. А.
Russian Federation
ogorodova@med-gen.ruKadyshevV. V.КадышевВ. В.
Russian Federation
ogorodova@med-gen.ruPolyakovA. V.ПоляковА. В.
Russian Federation
ogorodova@med-gen.ruResearch Centre for Medical GeneticsМедико-генетический научный центр им. академика Н.П. Бочкова11042024604698326022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/666948

Inherited retinal diseases (IRDs) are a clinically heterogeneous group of retinal pathologies associated with vision loss due to dysfunction or degeneration of photoreceptor and retinal pigment epithelium. Autosomal recessive forms of IRDs account for more than 55% of all diseases in this group on average worldwide. This study presents data on frequent pathogenic and likely pathogenic variants in recessive IRDs genes obtained from a retrospective analysis of high-throughput sequencing data from a large Russian cohort of patients with suspected hereditary non-syndromic retinal pathology. Data from 1470 unrelated patients were analyzed. Pathogenic and likely pathogenic variants were identified in the zygosity required for the development of the diseasein 643 patients (43.74%). It was found that 9 genes (ABCA4, CNGB3, USH2A, RPE65, CRB1, CNGA3, CEP290, GUCY2D, PDE6H) account for 73.3% of all molecularly confirmed cases of IRDs in Russian patients. An analysis of the spectrum of nucleotide variants of these genes was carried out, and 17 variants were identified that occur with an allelic frequency of more than 1% for each gene. In light of obtained data, the diagnostic systems based on the multiplex ligation-dependent probe amplification reaction (MLPA) were developed. The informativity of the two systems for diagnosing autosomal recessive non-syndromic forms of inherited retinal diseases is 16.4%, the informativity for all forms of non-syndromic retinal diseases exceeds 7%. For a group of patients with achromatopsia, a study using one of the systems will make it possible to establish a diagnosis in 62.5% of cases.

Наследственные заболевания сетчатки (НЗС) представляют собой клинически гетерогенную группу патологий сетчатки, сопровождающихся потерей зрения вследствие дисфункции или дегенерации фоторецепторных клеток и клеток пигментного эпителия сетчатки. На долю аутосомно-рецессивных форм НЗС в среднем в мире приходится более 55% всех заболеваний этой группы. В настоящем исследовании представлены частые патогенные и вероятно патогенные варианты в генах, ответственных за аутосомно-рецессивные НЗС, полученные на основе ретроспективного анализа данных высокопроизводительного секвенирования большой российской когорты пациентов с подозрением на наследственную несиндромальную патологию сетчатки. Были проанализированы данные 1470 неродственных пациентов. У 643 (43,74%) были выявлены патогенные и вероятно патогенные варианты в зиготности, необходимой для развития заболевания. Установлено, что на долю девяти генов (ABCA4, CNGB3, USH2A, RPE65, CRB1, CNGA3, CEP290, GUCY2D, PDE6H) приходится 73.3% всех молекулярно-подтвержденных случаев НЗС у российских пациентов. Был проведен анализ спектров нуклеотидных вариантов данных генов и выявлено 17 вариантов, встречающихся с аллельной частотой более 1% для каждого из генов. На основании полученных данных были разработаны диагностические системы на основе аллель-специфичной мультиплексной проба-зависимой лигазной реакции (MLPA). Информативность двух систем для диагностики аутосомно-рецессивных несиндромальных форм наследственных заболеваний сетчатки составляет 16.4%, информативность для всех форм несиндромальных заболеваний сетчатки превышает 7%. Для группы пациентов с ахроматопсией исследование с использованием одной из систем позволит установить диагноз в 62.5% случаев.

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