pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLCpulmo-2817Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESДесятилетний опыт молекулярногенетической диагностики муковисцидоза в МГНЦ РАМНTen years of molecular genetic diagnosis of cystic fibrosis in Russian patientsПетроваН. В.PetrovaN. V.

Москва

ГинтерЕ. К.GinterE. K.

Москва

Медико-генетический центр РАМНRussian Federation200130092001031720Copyright © Петрова Н.В., Гинтер Е.К., 20012001Петрова Н.В., Гинтер Е.К.Petrova N.V., Ginter E.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/2817

Молекулярно-генетическое исследование больных муковисцидозом (МВ) проводится в лаборатории генетической эпидемиологии МГНЦ РАМН с 1990 г. К настоящему времени молекулярно-генетический анализ выполнен в 466 семьях, имеющих больного МВ ребенка. Предварительное клиническое обследование и постановка диагноза проводились в научно-клиническом отделении муковисцидоза МГНЦ РАНМ. Более 80% пациентов проживали в Европейской части России, около 15% – из районов Сибири и Дальнего Востока. ДНК больных и их родителей проскринировали на 17 мутаций в гене CFTR. Относительные частоты 13 обнаруженных мутаций следующие: ∆Р508 – 53%, CFTRdele2,3(21кЬ) – 6,4%, N1303К – 2,6%, G542Х – 2,0%, W1282Х – 1,9%, 3849+10кbС-Т – 1,9%, 2143∆Т – 1,8%, 2184insА – 1,8%, R334W – 0,7%, S1196Х – 0,7%, 1677∆ТА – 0,5%, 394∆ТТ – 0,4%, G551D – 0,3%. Кажется вероятным, что возможно выделить ядро частых “славянских” мутаций в изученной выборке МВ хромосом: СFTRdele2,3(21кЬ), 2143∆Т, 2184insA, но их происхождение и история распространения требуют дальнейшего исследования и уточнения. Примерно в 25% муковисцидозных хромосомах мутация остается неидентифицированной, поэтому в семьях, где один или оба родителя являются носителями неидентифицированных мутаций, проводится анализ внутри- и внегенных ДНК-маркеров для определения фазы сцепления мутантного МВ-аллеля. В результате информативность косвенного теста в семьях, имеющих больного МВ ребенка, достигает 100%.

Since 1990 466 OF patients and more than 1000 members of their families which were clinically diagnosed in the Department of OF of the Research Centre for Medical Genetics have been examined for 20 mutations in the CFTR gene. More than 80% of the patients were originated from the European part of Russia. The relative frequencies of 13 screened OF mutations were as follows: AF508 — 53%, CFTkdele2.3(21kb) – 6.4%, N1303K – 2.6%, G542X – 2.0%, W1282X – 1.9%, – 3849+1 OkbC-T – 1.9%, 2143AT – 1.8%, 2184insA – 1,8%, R334W – 0.7%, S1196X – 0.7%, 394ATT – 0.4%, 1677ATA – 0.5%, G551D – 0.3%. Other screened mutations have not been identified in our sample. The above mentioned 13 mutations account for 75% of all OF alleles of Russian patients. It seems that it is possible to distinguish a nucleos of common “Slavic” mutations (CFTRdele2.3(21kb), 2143AT, 21S4insA) but their origin and history of distribution should be clarified further. Still about 25% of OF alleles are remained to be identified in Russian- population and only for 56% of OF patients the full OF genotype could be recognized. In families where one or both parents have unidentified mutations analysis of inter- andintragenic DNA markers have been exploited to complete genetic testing. As a result the informativity close to 100% could be obtained for all families with the OF child.

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