Three RET germ-line mutations in a family with multiple endocrine neoplasia type 2A syndrome

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Abstract


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.


Natalia V Severskaya

Author for correspondence.
severskn@mrrc.obninsk.ru
A.Tsyb Medical Radiological Research Centre - branch of the National Medical Research Radiological Centre, Obninsk
Russian Federation

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

Vladimir G Polyakov

vgp-04@mail.ru
N.N. Blokhin Russian Cancer Research Center, Moscow; Russian Medical Academy of Postgraduate Education, Moscow
Russian Federation

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

Ruslan V Shishkov

rvshishkov@mail.ru
N.N. Blokhin Russian Cancer Research Center, Moscow; Russian Medical Academy of Postgraduate Education, Moscow
Russian Federation

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

Alexey A Ilin

ilyin@mrrc.obninsk.ru
A.Tsyb Medical Radiological Research Centre - branch of the National Medical Research Radiological Centre, Obninsk
Russian Federation

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

Natalia V Ivanova

nv.ivanova6@gmail.com
N.N. Blokhin Russian Cancer Research Center, Moscow
Russian Federation

к.м.н., врач

Alevtina I. Pavlovskaya

fake@endojournals.ru
N.N. Blokhin Russian Cancer Research Center, Moscow
Russian Federation

MD, PhD

Valentina M. Kozlova

fake@endojournals.ru
N.N. Blokhin Russian Cancer Research Center, Moscow; Research Centre for Medical Genetics, Moscow
Russian Federation

MD

Faina A. Amosenko

fake@endojournals.ru
N.N. Blokhin Russian Cancer Research Center, Moscow; Research Centre for Medical Genetics, Moscow
Russian Federation

вед.н.с., к.б.н.

Liudmila N. Lyubchenko

fake@endojournals.ru
N.N. Blokhin Russian Cancer Research Center, Moscow
Russian Federation

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

Tatyana P. Kazubskaya

fake@endojournals.ru
N.N. Blokhin Russian Cancer Research Center, Moscow
Russian Federation

ст.н.с., д.м.н.

Natalia A. Koshechkina

kosh_n_a@mail.ru
N.N. Blokhin Russian Cancer Research Center, Moscow; Russian Medical Academy of Postgraduate Education, Moscow
Russian Federation

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

Elena V. Mikhailova

elena_1357@mail.ru
N.N. Blokhin Russian Cancer Research Center, Moscow
Russian Federation

к.м.н., зав. рентгенодиагностическим отделением

Irina I. Matveeva

severskn@mrrc.obninsk.ru
N.N. Blokhin Russian Cancer Research Center, Moscow
Russian Federation

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

Irina N. Serebryakova

severskn@mrrc.obninsk.ru
N.N. Blokhin Russian Cancer Research Center, Moscow
Russian Federation

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

Svetlana N. Mikhailova

astra-sn@mail.ru
N.N. Blokhin Russian Cancer Research Center, Moscow
Russian Federation

зав. поликлиническим отд.

Natalia Y. Kalinchenko

kalinnat@rambler.ru
N.N. Blokhin Russian Cancer Research Center, Moscow; Endocrinology Research Centre, Moscow
Russian Federation

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

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Copyright (c) 2017 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.

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