medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2018.01.41-49medgen-382Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHАутосомные реципрокные транслокации: пренатальная селекция, сегрегация и оценка эмпирического риска рождения жизнеспособного ребенка с хромосомным дисбалансом при семейном носительствеAutosomal reciprocal translocations: prenatal selection, segregation and assessment of empirical risks for reciprocal translocation carriers of having a liveborn child with chromosome imbalanceШиловаН. В.ShilovaN. V.nvsh05@mail.ruФГБНУ «Медико-генетический научный центр»РоссияFederal State Budgetary Institution «Research centre for Medical Genetics»Russian Federation2018260320181714149Copyright © Шилова Н.В., 20182018Шилова Н.В.Shilova N.V.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/382

Аутосомные реципрокные транслокации (АРТ), являются наиболее частой структурной хромосомной перестройкой. Носители АРТ имеют повышенный риск рождения детей с хромосомным дисбалансом, который может варьировать от низкого до высокого в зависимости от характеристик транслокации и типа патологической мейотической сегрегации. Целью исследования являлся анализ пренатальной селекции, мейотической сегрегации и оценка эмпирического риска рождения жизнеспособного ребенка с хромосомным дисбалансом у 49 носителей АРТ. Оценка пахитенной диаграммы проводилась для каждой транслокации на основании количественных характеристик мейотического квадривалента. Наблюдаемый и ожидаемый хромосомный дисбаланс при всех типах патологической сегрегации оценивался в процентах от гаплоидной длины аутосом. Оценка жизнеспособности плодов и потенциальных зигот с хромосомным дисбалансом проводилась с использованием модели, основанной на измерении хромосомных сегментов дистальнее точек разрывов и определении относительного размера хромосомного дисбаланса. Установлена тенденция к преимущественной пренатальной селекции зигот вследствие альтернативного типа сегрегации АРТ. Показано, что анализ количественных характеристик квадривалента и пахитенной диаграммы позволяет оценить тип патологической мейотической сегрегации, приводящей к наименьшему хромосомному дисбалансу, и риск формирования несбалансированных гамет. Определено, что оценка жизнеспособности зигот, основанная на сопоставлении относительного размера несбалансированных хромосомных сегментов, может быть дополнительным этапом при установлении повторного риска рождения ребенка с хромосомной патологией у носителей АРТ. В 80% случаев транслокаций риск рождения жизнеспособного ребенка с хромосомным дисбалансом расценивается как низкий. Мейотическая сегрегация хромосом у носителей АРТ происходит с преимущественным формированием и последующей пренатальной селекцией зигот вследствие альтернативного, непатологического типа сегрегации. Для каждой транслокации необходимо проводить оценку наиболее вероятного типа патологической сегрегации и жизнеспособности плодов или новорожденных. Эмпирический риск не может быть использован как единственный и решающий фактор при оценке повторного риска рождения жизнеспособного ребенка с хромосомным дисбалансом.

Autosomal reciprocal translocations are among the most frequent chromosomal rearrangements in man. Though phenotypically normal, the carrier of reciprocal translocation may be at increased risk of having a chid with multiple malformations and mental retardation due to malsegregation at meiosis resulting in gametes with chromosome imbalance. An accurate estimate of the probability of this event is understandably desirable. Aim. The aim of this investigation was an analysis of prenatal selection, meiotic segregation and assessment of empirical risks for reciprocal translocation carriers of having a liveborn child with unbalanced karyotype on 49 reciprocal translocation carriers. Materials and Methods. The pachytene diagrams were analyzed for each translocation taking in account the exact lengths of the chromosomes involved. The observed and most probable unbalanced segments were evaluated using the Chromosome Imbalance Size-Viability Model and Surface of Viable Unbalances consisting of the measurement of chromosomal segments distal to the breakpoints expressed in percentage of haploid autosomal length - %HAL. Results. The tendency to preferential prenatal selection of zygotes is established due to the 2:2 alternate segregation. It is shown that the analysis of quantitative characteristics of quadrivalent and pachytene diagram allows to estimate the type of malsegregation producing the smallest imbalance and the risk of formation of unbalanced gametes. Evaluation of viability of zygotes may be an additional step in establishing of the recurrence risks. In 80% of cases the risk of a viable child with a chromosomal imbalance is regarded as low. Conclusions. Meiotic segregation of chromosomes in carriers of autosomal reciprocal translocations occurs with preferential formation and subsequent prenatal selection of zygotes due to alternate segregation. It is necessary to assess segregation giving the smallest imbalance and viability of the imbalance. Empirical risk was not found to be useful as a discriminating risk predictor in individual genetic counselling.

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