medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.04.25-37medgen-2460Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHКлиническое значение определения размеров нуклеотидной экспансии гена HTT у пациентов с болезнью ГентингтонаClinical significance of the size of nucleotide expansion of the HTT gene in patients with Huntington’s diseaseДевяткинаЕ. А.DeviatkinaE. A.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8

6-8 L’va Tolstogo st., Saint Petersburg, 197022

e.deviatkina@list.ruНазаровВ. Д.NazarovV. D.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8

6-8 L’va Tolstogo st., Saint Petersburg, 197022

СидоренкоД. В.SidorenkoD. V.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8

6-8 L’va Tolstogo st., Saint Petersburg, 197022

МусоноваА. К.MusonovaA. K.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8

6-8 L’va Tolstogo st., Saint Petersburg, 197022

ЛапинС. В.LapinS. V.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8

6-8 L’va Tolstogo st., Saint Petersburg, 197022

БлиноваТ. В.BlinovaT. V.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8

6-8 L’va Tolstogo st., Saint Petersburg, 197022

СурковаЕ. А.SurkovaE. A.

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8

6-8 L’va Tolstogo st., Saint Petersburg, 197022

ФГБОУ ВО Первый Санкт-Петербургский государственный медицинский университет им. И.П. Павлова Минздрава РФРоссияI.P. Pavlov First Saint Petersburg State Medical UniversityRussian Federation2024130720242342537Copyright © Девяткина Е.А., Назаров В.Д., Сидоренко Д.В., Мусонова А.К., Лапин С.В., Блинова Т.В., Суркова Е.А., 20242024Девяткина Е.А., Назаров В.Д., Сидоренко Д.В., Мусонова А.К., Лапин С.В., Блинова Т.В., Суркова Е.А.Deviatkina E.A., Nazarov V.D., Sidorenko D.V., Musonova A.K., Lapin S.V., Blinova T.V., Surkova E.A.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/2460

Цель: описание клинической значимости определения числа CAG-повторов в экзоне 1 гена HTT у пациентов с болезнью Гентингтона в Российской Федерации.Методы. В исследование были включены образцы ДНК 1290 человек, обследованных для уточнения количества CAG-повторов в гене HTT в лаборатории диагностики аутоиммунных заболеваний НМЦ Минздрава России по молекулярной медицине ПСПбГМУ имени акад. И.П. Павлова. От каждого обследованного было получено информированное добровольное согласие. Всем обследованным было проведено исследование количества CAG-повторов в гене HTT методом ПЦР с праймингом тройных повторов и последующим разделением ПЦР продукта с использованием фрагментного анализа. В группу «Норма» были включены образцы, выявленное число повторов которых не превышает 26. Группа «Премутация» состояла из образцов, имевших хотя бы один аллель с числом повторов от 27 до 35. В группу «Мутация» включены образцы, число повторов которых больше или равно 36. Статистическая обработка проведена с использованием программы GraphPad Prism 8 (GraphPad Software Inc., США). Статистически значимыми считались различия при p<0,05. Для расчета корреляции была использована формула корреляции Пирсона.Результаты. В группу «Норма» вошли 659 обследованных. К группе «Премутация» были отнесены 44 обследованных. Группа «Мутация» включала в себя 587 обследованных. В группе Мутация была исследована взаимосвязь возраста молекулярногенетического подтверждения болезни и размера экспансионного аллеля и установлена обратная зависимость между данными параметрами (p<0,0001 r=-0,4930). В 15 из 32 семейных случаев ребенку передался аллель с экспансией. Передача мутации от отца произошла в 86,67% случаев, от матери – в 13,33% случаев.Заключение. Выявлена обратная зависимость между возрастом обращения в лабораторию и числом CAG-повторов. Выявленная распространенность аллелей с числом повторов от 27 до 35 включительно в популяции свидетельствует о необходимости изучения особенностей клинического течения болезни Гентингтона у их носителей.

Aim: to describe the clinical significance of the number of CAG repeats in exon 1 of the HTT gene in patients with Huntington’s disease in the Russian Federation.Methods. A total of 1290 DNA samples was obtained from previously collected samples of patients. The number of CAG repeats in the HTT gene was evaluated in the «Laboratory for diagnostics of autoimmune diseases» the Federal State Budgetary Educational Institution of Higher Education Academician I.P. Pavlov First St. Petersburg State Medical University of the Ministry of Healthcare of Russian Federation. Informed consent was obtained from each patient. To evaluate CAG-repeats number in HTT gene, fragment analysis and triplet repeat primed PCR were used. The «Normal» group included patients with number of CAG repeats ≤26. The «Premutation» group consisted of patients who had at least one allele with the number of triplets from 27 to 35 (intermediate alleles, IA). The «Mutation» group included patients with number of CAG repeats ≥36 . Statistical analysis was performed by using the GraphPad Prism 8 program (GraphPad Software Inc., USA).Results. A total of 659 samples had no expansion, 44 samples had at least one IA, 587 samples had ≥36 CAG repeats. In the «Mutation» group the association between the age of examination in the laboratory and the size of the expansion allele was investigated and an inverse correlation between these parameters was revealed (p< 0.0001 r= 0.4930). In 15 of 32 familial cases, the expansion allele was transmitted to the child. Transmission of the mutation from the father occurred in 86.67% of cases, from the mother − in 13.33% of cases.Conclusions. Inverse correlation was revealed between age of the patient’s first visit to laboratory and the number of CAG-repeats. The revealed prevalence of intermediate alleles in the population accentuates the importance of studying the characteristics of the clinical course of Huntington’s disease in their carriers.

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