problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl201662628-32problendo-7944Research ArticleКлинические случаиCase ReportsТри герминальные мутации в гене RET у членов одной семьи с синдромом множественных эндокринных неоплазий 2А типаThree RET germ-line mutations in a family with multiple endocrine neoplasia type 2A syndromeСеверскаяНаталья ВикторовнаSeverskayaNatalia V

кандидат медицинских наук, зав. отделением «ин витро» радионуклидной диагностики, врач эндокринолог

severskn@mrrc.obninsk.ruПоляковВладимир ГеоргиевичPolyakovVladimir G

доктор медицинских наук, академик РАН, заместитель директора и заведующий хирургическим отделением №1 (опухолей головы и шеи) НИИ ДОГ ФГБНУ «РОНЦ им. Н.Н. Блохина, заведующий кафедрой детской онкологии ГБОУ ДПО «РМАПО» МЗ РФ

vgp-04@mail.ruШишковРуслан ВладимировичShishkovRuslan V

д.м.н., проф. каф. детской онкологии ГБОУ ДПО «РМАПО» Минздрава России, врач хирургического отд. №1 (опухолей головы и шеи) НИИ ДОГ ФГБУ «РОНЦ им. Н.Н. Блохина» Минздрава России

rvshishkov@mail.ruИльинАлексей АмуровичIlinAlexey A

д.м.н., вед.н.с. отд. радиохирургического лечения закрытыми радионуклидами

ilyin@mrrc.obninsk.ruИвановаНаталья ВладимировнаIvanovaNatalia V

к.м.н., врач

nv.ivanova6@gmail.comПавловскаяАлентина ИвановнаPavlovskayaAlevtina I.

к.м.н., вед.н.с. паталогоанатомического отделения

MD, PhD

КозловаВалентина МихайловнаKozlovaValentina M.

врач-генетик лаборатории клинической онкогенетики

MD

АмосенкоФаина АркадьевнаAmosenkoFaina A.

вед.н.с., к.б.н.

ЛюбченкоЛюдмила НиколаевнаLyubchenkoLiudmila N.

д.м.н., зав. лабораторией клинической онкогенетики

КазубскаяТатьяна ПавловнаKazubskayaTatyana P.

ст.н.с., д.м.н.

КошечкинаНаталья АнатольевнаKoshechkinaNatalia A.

м.н., вед.н.с. рентгенодиагностического отделения НИИ ДОГ ФГБНУ «РОНЦ им. Н.Н. Блохина», проф. каф. детской онкологии РМАПО Минздрава России

kosh_n_a@mail.ruМихайловаЕлена ВладимировнаMikhailovaElena V.

к.м.н., зав. рентгенодиагностическим отделением

elena_1357@mail.ruМатвееваИрина ИвановнаMatveevaIrina I.

д.м.н., зав. группы детской гемоцитологии клинико-диагностической лаборатории централизованного клинико-лабораторного отдела

severskn@mrrc.obninsk.ruСеребряковаИрина НиколаевнаSerebryakovaIrina N.

к.м.н., врач клин. лаб. диагностики группы детской гемоцитологии клинико-диагностической лаборатории централизованного клинико-лабораторного отдела

severskn@mrrc.obninsk.ruМихайловаСветлана НиколаевнаMikhailovaSvetlana N.

зав. поликлиническим отд.

astra-sn@mail.ruКалинченкоНаталья ЮрьевнаKalinchenkoNatalia Y.

к.м.н., ст.н.с., врач детский эндокринолог

kalinnat@rambler.ruМедицинский радиологический научный центр им. А.Ф. Цыба — филиал ФГБУ «Национальный медицинский исследовательский радиологический центр» Минздрава РоссииРоссияA.Tsyb Medical Radiological Research Centre - branch of the National Medical Research Radiological Centre, ObninskRussian FederationФГБУ «Российский онкологический научный центр им. Н.Н. Блохина»; ГБОУ ДПО «Российская медицинская академия последипломного образования»РоссияN.N. Blokhin Russian Cancer Research Center, Moscow; Russian Medical Academy of Postgraduate Education, MoscowRussian FederationФГБУ «Российский онкологический научный центр им. Н.Н. Блохина»;РоссияN.N. Blokhin Russian Cancer Research Center, MoscowRussian FederationФГБУ «Российский онкологический научный центр им. Н.Н. Блохина»РоссияN.N. Blokhin Russian Cancer Research Center, MoscowRussian FederationФГБУ «Российский онкологический научный центр им. Н.Н. Блохина»; ФГБНУ «Медико-генетический научный центр»РоссияN.N. Blokhin Russian Cancer Research Center, Moscow; Research Centre for Medical Genetics, MoscowRussian FederationФГБУ «Российский онкологический научный центр им. Н.Н. Блохина»; ФГБУ «Эндокринологический научный центр» Минздрава РоссииРоссияN.N. Blokhin Russian Cancer Research Center, Moscow; Endocrinology Research Centre, MoscowRussian Federation2016120120176262832Copyright © Северская Н.В., Поляков В.Г., Шишков Р.В., Ильин А.А., Иванова Н.В., Павловская А.И., Козлова В.М., Амосенко Ф.А., Любченко Л.Н., Казубская Т.П., Кошечкина Н.А., Михайлова Е.В., Матвеева И.И., Серебрякова И.Н., Михайлова С.Н., Калинченко Н.Ю., 20162016Северская Н.В., Поляков В.Г., Шишков Р.В., Ильин А.А., Иванова Н.В., Павловская А.И., Козлова В.М., Амосенко Ф.А., Любченко Л.Н., Казубская Т.П., Кошечкина Н.А., Михайлова Е.В., Матвеева И.И., Серебрякова И.Н., Михайлова С.Н., Калинченко Н.Ю.Severskaya N.V., Polyakov V.G., Shishkov R.V., Ilin A.A., Ivanova N.V., Pavlovskaya A.I., Kozlova V.M., Amosenko F.A., Lyubchenko L.N., Kazubskaya T.P., Koshechkina N.A., Mikhailova E.V., Matveeva I.I., Serebryakova I.N., Mikhailova S.N., Kalinchenko N.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/7944

Встречаемость одновременно нескольких герминальных мутаций в гене RET у больных с синдромом множественных эндокринных неоплазий 2А типа (МЭН 2А) крайне редка. При обследовании родственников больных с синдромом МЭН 2А обычно исследуют только один экзон, в котором ранее была выявлена характерная для данной семьи мутация. Однако вторая мутация может изменять фенотип пациентов с синдромом МЭН 2А, включая возраст клинического проявления медуллярного рака щитовидной железы (МРЩЖ) и пенетрантность феохромоцитомы. Приводится описание семьи с синдромом МЭН2А, у членов которой выявлены различные комбинации трех мутаций гена RET (RET кодон C634R, C634R+I852M, I852M+Y791F, Y791F). Минимальный срок манифестации МРЩЖ отмечен при комбинации C634R+I852M (в 24 года). У больного с мутацией C634R, оперированного по поводу МРЩЖ в 35 лет, на момент обследования в 49 лет имелись признаки персистенции заболевания. Носитель мутации Y791F в 28 лет клинически здоров. У ребенка с мутацией I852M+Y791F при профилактической тиреоидэктомии в 4 года выявлена С-клеточная гиперплазия. Клиническое значение сочетанных мутаций в данной семье не определено. Представлен краткий обзор литературы по множественным мутациям в гене RET у больных МРЩЖ и синдромом МЭН 2А.

Multiple mutations in RET proto-oncogene are not common findings in patients with multiple endocrine neoplasia type 2A syndrome (MEN2A). Screening for RET mutation in MEN2A family members is usually limited by the known affected exon. However the second unrevealed mutation in RET proto-oncogene can coexist and modify the phenotype of MEN2 patients, including age of onset of medullary thyroid carcinoma, penetrance of pheochromocytoma etc. We here describe a family with MEN 2A syndrome with combination of three different germ-line RET mutations in its members (RET codon C634R, C634R+I852M, I852M+Y791F, Y791F). The earliest onset of medullary thyroid carcinoma was in a patient harboring the C634R+I852M double mutation at age 24 years. A 49-y.o.patient with C634R mutation has persistent medullary thyroid carcinoma after thyroidectomy at 35 years old. A carrier of Y791F mutation had no clinical evidence of disease at age of 28 years. In a child with compound I852M+Y791F mutation preventive thyroidectomy revealed C-cell hyperplasia at age of 4 years. The clinical significance of double RET mutation in the described family is not clear. Literature data of multiple germ-line RET mutations in patients with multiple endocrine neoplasia type 2A syndrome are presented.

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