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ИННОВАЦИОННЫЕ ТЕХНОЛОГИИ В ПЕДИАТРИИ И ДЕТСКОЙ ХИРУРГИИ
ity. Additionally, constitutional chromothripsis is shown to affect the brain in a non-malignant disease. Thus, constitutional chromosome instability in the brain is likely to be a mechanism for neuropathology in this devastating neuropsychiatry disease. Supported by the Russian Science Foundation (Grant #14-35-00060).
CYTOGENETICALLY VISIBLE COPY NUMBER VARIATIONS (CG-CNVS) IN BANDING AND MOLECULAR CYTOGENETICS OF HUMAN; ABOUT HETEROMORPHISMS AND EUCHROMATIC VARIANTS Liehr T.
Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany
Copy number variations (CNVs) having no (obvious) clinical effects were rediscovered as major part of human genome in 2004. However, for every cytogeneticist microscopically visible harmless CNVs (CG-CNVs) are well known since decades. Harmless CG-CNVs can be present as heterochromatic or even as euchromatic variants in clinically healthy persons. Here I provide a review on what is known today on the still too little studied harmless human CG-CNVs, point out which can be mixed up with clinically relevant pathological CG-CNVs and shortly discuss that the artificial separation of euchromatic submicroscopic CNVs (MG-CNVs) and euchromatic CG-CNVs is no longer timely. Overall, neither so-called harmless heterochromatic nor so-called harmless euchro-matic CG-CNVs are considered enough in evaluation of routine cytogenetic analysis and reporting. This holds especially true when bearing in mind the so-called two-hit model suggesting that combination of per se harmless CNVs may lead to clinical aberrations if they are present together in one patient.
MYELODYSPLASTIC SYNDROME WITHOUT RING SIDEROBLASTS AND WITH JANUS KINASE 2 GENE MUTATION: AN UNUSUAL CASE REPORT
Ornellas M.H.12, de Franga Silva M.1, Solza C.3, de Lucena Gongalves S.B.S.3, de Almeida L.S.1,2, de Paula Ayres Silva J.4, Seixas T.L.5, Bastos E.F.5,6, Liehr T.7, Alves G.1,2,8 'Department of Pathology, Laboratory of Circulating Markers, Faculty of Medica Sciences (FCM), Rio de Janeiro, Brazil;
2Graduation Course in Medical Sciences, Faculty of Medica Sciences (FCM), Rio de Janeiro, Brazil; 3Department of Haematology, Pedro Ernesto University Hospital (HUPE), Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil;
"Department of Pathology, Oswaldo Cruz Institute (IOC), Ministry of Health, Rio de Janeiro, Brazil; 'Cytogenetics Laboratory, Faculty of Medical Sciences, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil;
•Department of Medical Genetic, Fernandes Figueira
Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil;
'University Clinic Jena, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany; 8Research Coordination, National Cancer Institute (INCA), Ministry of Health, Rio de Janeiro, Brazil
Myelodysplastic syndrome (MDS) cases comprise a heterogeneous group of hematological disorders that are characterized by impaired hematopoiesis, with cytopenias of different grades and risk of developing acute myeloid leukemia. MDS may rarely be associated with thrombocy-tosis. In such cases, myelodysplasia and myeloproliferative disorders may overlap, making correct diagnosis difficult. We herein describe a case of MDS with thrombocytosis, Janus kinase 2 gene mutation positive and Perls' staining negative, which was initially classified as essential throm-bocythemia (ET). This case highlights that MDS may be misdiagnosed as ET and inappropriate treatment may be initiated. Therefore, it is crucial to carefully combine all available data on morphology and immunophenotyp-ing, and to perform the necessary molecular, cytogenetic and molecular cytogenetic analyses, in order to correctly diagnose this disease.
A NEW COMPLEX KARYOTYPE IN A UNIQUE DE NOVO MYELODYSPLASTIC SYNDROME CASE INVOLVING TEN CHROMOSOMES AND MONOAL-LELIC LOSS OF TP53
Wafa A.1, As'sad M.1, Liehr T.2, Aljapawe A.3, Al Achkar W.1
'Molecular Biology and Biotechnology Department, Human Genetics Div., Chromosomes lab., Atomic Energy Commission of Syria, Damascus, Syria; Jena University Hospital, Institute of Human Genetics, Jena, Germany;
3Molecular Biology and Biotechnology Department, Mammalians Biology Div., Flow-cytometry Lab., Atomic Energy Commission of Syria, Damascus, Syria
Myelodysplastic syndrome (MDS) is a group of clonal stem cell disorders characterized by cytopenia, dyspla-sia in one or more cell lineages, and ineffective hemato-poiesis. MDS is associated with high risk of progression to acute myeloid leukemia. At initial diagnosis, clonal cytogenetic aberrations are present in 40—70% of patients with de novo (primary) MDS and in 65—95% of patients with therapyassociated ones (t-MDS). Most commonly observed abnormalities present in MDS are monosomy 5 and 7, trisomy 8, deletions of long arm of chromosome 20 as well as complex karyotypes. Loss or gain of chromosomal material is known to be related to disease development and progression. In a de novo adult MDS case banding cytogenetics, refined by array-proven multicolor banding (aMCB) revealed a unique complex karyotype involving ten chromosomes that include del(5q), del(7q), deletions in parts of both chromosomes 10, and a dic(7;17). Interestingly, the dic(7;17) leads to monosomy of the tu-
РОССИЙСКИЙ ВЕСТНИК ПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 4, 2016 ROSSIYSKIY VESTNIK PERINATOLOGY IPEDIATRII, 4, 2016
Раздел 6. Наследственные заболевания и врожденные пороки развития
mor suppressor gene TP53. The patient had an immuno-phenotype consistent with refractory anemia with excess blasts in transformation (RAEB-t) according to French— American—British (FAB) classification. To the best of our knowledge, a comparable adult MDS case associated with such a complex karyotype and loss of TP53 was not previously reported. As most of complex aberrations were found simultaneously in all studied malignant cells this may be a hint on an initial one step development of this complex rearrangement by chromothripsis.
PARTIAL TRISOMY 1q21-qter AND PARTIAL MONOSOMY 7q21-qter DUE TO A DERIVATIVE CHROMOSOME 7 IN MYELODYSPLASTIC SYNDROME ASSOCIATED WITH SQUAMOUS CELL CARCINOMA: CASE STUDY
Wafa A.1, Moassass F.1, Liehr T.2, Aljapawe A.3, Al Achkar W.1
'Molecular Biology and Biotechnology Department, Human Genetics Div., Chromosomes lab., Atomic Energy Commission of Syria, Damascus, Syria; 2Jena University Hospital, Institute of Human Genetics, Jena, Germany;
3Molecular Biology and Biotechnology Department, Mammalians Biology Div., Flow-cytometry Lab., Atomic Energy Commission of Syria, Damascus, Syria
Myelodysplastic syndrome (MDS) comprises a group of clonal stem cell disorders characterized by cytopenia, dysplasia in one or more hematopoietic cell lineages, and ineffective hematopoiesis leading to bone marrow failure, leukemic transformation, and clonal cytogenetic aberrations. These disorders are associated with a high risk of progression to acute myeloid leukemia and thus an overall short survival. Cytogenetic studies play a major role in confirmation of diagnosis and prediction of clinical outcome, and have contributed to the understanding of its pathogenesis. The most common chromosomal abnormalities in MDS include complete and partial mono-somy of chromosomes 5 and 7, deletion of 20q and 12p, trisomy 8, and 11q23 aberrations. A less frequent but non-random chromosomal abnormality in MDS is partial tri-somy involving parts of chromosome 1q. We report a new adult MDS case associated with squamous cell carcinoma (SCC). Banding cytogenetics, refined by array-proven multicolor banding (aMCB) revealed an unbalanced translocation der(7)t(1;7)(q21;q21), which led to partial trisomy of 1q and partial monosomy of 7q as yet unreport-ed clonal abnormality. The case had an immunopheno-type consistent with refractory anemia with excess blasts (RAEB-2) according to French-American-British (FAB) classification. To the best of our knowledge, this is the first adult MDS case associated with SCC and an unbalanced translocation t(1;7). As previously reported similar cases, the present one also is a male MDS with a translocation t(1;7), which provides to the suspicion of a gender association of this cytogenetic MDS subgroup.
КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ СИНДРОМА ШПРИНТЦЕНА-ГОЛДБЕРГ, ОБУСЛОВЛЕННОГО МУТАЦИЕЙ (NM_0030.36(SKI):C.92C>T(P. SER31LEU) В ПЕРВОМ ЭКЗОНЕ ГЕНА SKI), У РЕБЕНКА С МАРФАНОПОДОБНЫМ ФЕНОТИПОМ И ЗАДЕРЖКОЙ ПСИХОРЕЧЕВОГО РАЗВИТИЯ Булатникова М.А., Василишина А.А., Котелевская Е.А., Куранова М.Л., Ларионова В.И. Медицинский центр «Покровский» OOO «Покровского банка»; Кафедра педиатрии с курсом кардиологии Северо-Западного государственного университета им. ак. Мечникова
Синдром Шпринтцзена—Голдберг — редкий генетический синдром, характеризуется ассоциацией марфаноподобого фенотипа с выраженной арахно-дактилией, задержкой психоречевого развития, но-зоспецифическим комплексом краниофациальных микроаномалий и краниосиностозом в классической форме. В настоящее время наличие краниосиносто-за является высокопатогномоничным, но не обязательным признаком синдрома. Известным геном, в котором мутации в гетерозиготном состоянии обуславливают развития синдрома является ген SKI. Все известные мутации в гене SKI сосредоточены в 1ом экзоне, что объясняется высокой специализацией функции отдельных доменов белка, кодируемого этим геном. Мы описываем мальчика 13 лет, консультированного генетиком в связи с предположением неверифицированного генетического синдрома: сочетание марфаноподобного фенотипа, выраженных краниофациальных микроаномалий, умеренной задержки психоречевого развития, деформации грудной клетки в сочетании с платиспонди-лией, прогрессирующим кифосколиозом, осложненным корешковым синдромом. «Необычные» лицо и телосложение отмечено родителями с первых лет жизни. К 4ем годам установлена задержка психоречевого развития, с 8 лет посещает коррекционную школу. Задержка психоречевого развития не сопровождается психоэмоциональными расстройствами. Ребенок — доброжелательный, контактный, стремящийся к общению со сверстниками, старательный в учебе. С 7—8 лет родители отмечают усугубление деформации грудной клетки, диспропорции между ростом и весом, изменения лица, а также появление кифосколиоза грудопоясничного отдела. В связи с наличием экзофтальма был исключен гипертиреоз, расходящееся косоглазие отмечено окулистом. С 9 лет — прогрессирование кифосколиоза, с 10—14 — развития пареза правой ноги, энурез. При нашем осмотре: марфаноподобное телосложение с резко выраженной арахнодактилией; крани-офациальные микроаномалии: лицо уплощенное (за счет высокого прямого лба, низкой спинки носа, уплощенной области носогубного желобка), микро-
РОССИЙСКИЙ ВЕСТНИК ПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 4, 2016 ROSSIYSKIY VESTNIK PERINATOLOGY IPEDIATRII, 4, 2016
