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ИННОВАЦИОННЫЕ ТЕХНОЛОГИИ В ПЕДИАТРИИ И ДЕТСКОЙ ХИРУРГИИ
dup(18)(q21.2q21.2) with the DCC gene was present in 9% of the cases, and the CDK6 gene in 7q21.2 was deleted in 12% of the here in detail studied ALL cases. In conclusion, high resolution molecular cytogenetic tools and molecular approaches like MLPA and aCGH need to be combined in a cost-efficient way, to identify disease and progression causing alterations in ALL, as majority of them are cryptic in banding cytogenetic analyses. This work was supported in parts by DAAD (fellowship to MAKO and PROBRAL 57054562 to TL) and CAPES (419/14 to MLMS).
INTEGRATED GENE MAPPING AND SYNTENY STUDIES GIVE INSIGHTS INTO THE EVOLUTION OF A SEXUAL PROTO-CHROMOSOME IN SOLEA SENEGALENSIS: TESTING INNOVATIVE MOLECULAR CYTOGENETIC APPROACHES FOR BASIC AND DIAGNOSTIC RESEARCH
Portela-Bens S.1, Merlo M.A.1, Rodriguez M.E.1, Cross I.1, Manchado M.2, Kosyakova N.3, Liehr T.3, Rebordinos L.1
'Área de Genética, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, Cádiz, Spain 2Centro IFAPA "El Toruño", Cádiz, Spain 3Institut für Humangenetik, Universitätsklinikum Jena, Jena, Germany
The evolution of genes related to sex and reproduction in fish shows high plasticity; and, to date, the sex determination system has not been identified in more than a few species. Sex determination and sexual differentiation are closely related because genetic and environmental factors work together in a hierarchical network to produce either male or female phenotypes. Solea senegalensis has 42 chromosomes in pairs, and an XX/XY chromosome system for sex determination, while related species show the ZZ/ZW system. Eleven candidate genes involved in these processes (dmtrl, dmtr2, dmtr3, sox3, sox6, sox, sox9, lh, cya19a1a, amh, vasa, aqp3, and nanos3) have been studied. Sequencing produced 56 contigs, from which 93 genes could be annotated. By including 9 previous mapped? bacterial artificial chromosomes (BACs) and one containing the fshß gene an integrated map has been produced, in which 15 pairs out of 21 have at least one BAC, important for distinguishing those chromosomes of S. senegalensis being similar in shape and size. The sequenced size of the 21 BACs represents about 10 % of the total size of the genome of Senegalensis. Multicolor fluorescence in situ hybridization (mFISH) showed the following co-locations in the same chromosomes: dmrt1-dmrt2-dmrt3, dmtr4-sox9-thrß, aqp3-sox8, cyp19a1a-fshß, igsf9b-sox3 and lysg-sox6. Synteny studies showed that the co-location of dmrt1-dmrt2-drmt3 in the largest metacentric chromosome of S. senegalensis is coincident with the Z chromosome of Cynoglossus semilaevis — a finding that would make this potentially a proto-sex-ual chromosome. Phylogenetic studies of 11 concatenated candidate genes show the close proximity of S. senegalensis to Danio rerio, in which temperature during early life determines sex. Comparative mapping with other species provides evidence of the preferential association of these candidate genes in particular chromosomes, instead of random
distribution. This suggests a mechanism for the selection of blocks of genes, with important repercussions in other species. This study has been supported by the Spanish Ministerio de Ciencia e Innovación MICINN (AGL 2011-25596) and by the AQUAGENET project (SOE 2/P1/E287) from the INTERREG IVB SUDOE program. SPB received a fellowship from the UCA.
A CRYPTIC THREE-WAY TRANSLOCATION T(10;19;11)(P12.31;Q13.31;Q23.3) WITH A DERIVATIVE Y-CHROMOSOME IN AN INFANT WITH ACUTE MYELOBLASTIC LEUKEMIA (M5B)
Rittscher K.1, Othman M.A.K.1, Vujic D.2-3, ZZecevic Z.3, Durisic M.3, Slavkovic B.3, Meyer B.4, Liehr T.1
'Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany 2University of Belgrade Faculty of Medicine, Belgarde, Serbia
3Mother and Child Health Care Institution of Serbia "Dr. Vukan Cupic", Belgrade, Serbia 4ZytoVision GmbH, Bremerhaven, Germany
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the malignant transformation of hemato-poietic precursors to a pathogenic cell clone. Chromosomal band 11q23 harboring MLL (= mixed lineage leukemia) gene is known to be involved in rearrangements with variety of genes as activating partners MLL in different AML subtypes. Overall, an unfavorable prognosis is associated with MLL abnormalities. Here we investigated an 11-month-old male presenting with hyperleukocytosis being diagnosed with AML subtype FAB-M5b. In banding cytogenetics a der(19)t(19;?)(q13.3;?) and del(Y)(q11.23) were found as sole aberrations. Molecular cytogenetics revealed that the MLL gene was disrupted and even partially lost due to a t(10;19;11)(p12.31;q13.31;q23.3), an MLL/MLLT10 fusion appeared, and the der(Y) was an asymmetric inverted duplication with breakpoints in Yp11.2 and Yq11.23. The patient got hematopoietic stem cell transplantation from his haploidentical mother. Still three months afterwards 15% of blasts were detected in bone marrow and later patient was lost during follow up. The present case highlights the necessity to exclude MLL rearrangements, even when there seems to be no actual hint from banding cytogenetics. Supported in parts by the DAAD.
COMPLEX CHROMOSOMAL REARRANGEMENTS IN PERIPHERAL BLOOD AND DECREASED AMOUNT OF NATURAL KILLER CELLS IN TWO FEMALE GAS STATION ATTENDANTS OF RIO DE JANEIRO
Santiago F.1'2'3, Lima S.1, Pinheiro T.1, Tavares S.R.1A3, Otero U.B.4, Tabalipa M.M.4, Kosyakova N.5, Ornellas M.H.12, Liehr T.5, Alves GM3
1Laboratório de Marcadores Circulantes, Departamento de Patologia e Laboratórios, Faculdade de Ciencias Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil 2Pós-graduagao em Ciencias Médicas (PGCM),
РОССИЙСКИЙ ВЕСТНИКПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 4, 2015
Раздел 2 Педиатрия
Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil
3Coordenagao de Pesquisa, Instituto Nacional de Cáncer, Rio de Janeiro, Brasil
4Unidade Técnica de Exposigao Ocupacional, Ambiental e Cáncer, Coordenagao de Prevengao e Vigilancia, Instituto Nacional de Cáncer, Rio de Janeiro, Brasil
5Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany
Brazilian gas station workers are chronically exposed to BTX (benzene, toluene, xylene) during their working time. Acquired chromosomal changes including complex chromosome rearrangements (CCR) were identified in two female attendants by fluorescence in situ hybridization, applying whole chromosome paints for chromosomes 1, 2 and 4. Lower natural killer (NK) cells count was also studied in the corresponding cases, highlighting a rare type of NK (NK-bright) in their peripheral blood cells. It is known that acquired chromosomal aberrations are positively correlated with cancer and reproductive risk. In concordance, lower NK cyto-toxicity increases the risk for cancer, as well. This is the first study providing hints on a possible causative relation of lower NK cytotoxicity and increase rates of chromosomal rearrangements including CCRs. Thus, the early identification of CCRs and blood abnormalities are necessary for effective genetic counseling of workers exposed to BTX, preventing diseases in workers themselves and also in their offspring.
PRENATAL SCREENING OF CYTOGENETIC ANOMALIES - A WESTERN INDIAN EXPERIENCE
Sheth F, Rahman M, Liehr T, Desai M, Patel B, Modi C, Trivedi S, Sheth J.
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena, Germany
Children born with congenital anomalies present a very high rate of perinatal death and neonatal mortality. Cytogenetic analysis is a convincing investigation along with clinical suspicion and biochemical screening tests. The current study was designed to characterize the prevalence and types of chromosomal abnormalities in high risk prenatal samples using different cytogenetic techniques. This study was conducted on a total of 1,728 prenatal samples (1,324 amniotic fluids, 366 chorionic villi and 38 cord blood samples) from 1994 to 2014 at Institute of Human Genetics, Ahmedabad, India. Conventional karyotyping was conducted with GTG-banding. Molecular approaches were used (fluorescence in situ hybridization = FISH and/or array-comparative ge-nomic hybridization = aCGH) when indicated to detect karyotypic abnormalities. Abnormal karyotypes were detected in 125/1,728 (7.2%) cases. Trisomy 21 was the most common abnormality detected in 46 (2.7%) followed by trisomy 18 in 11 (0.6%) and trisomy 13 in 2 (0.1%) samples. Besides, structural abnormalities such as reciprocal and Robertsonian translocation were detected in 20 [1.2%] cases. Turner syndrome was diagnosed in seven (0.4%) cases; in six (0.34%) cases there was an inversion in the Y-chromosome. Hetero-morphic variants were diagnosed in 22 (1.3%) cases. Finally,
small supernumerary marker chromosomes (sSMC) were found in six (0.34%) cases. Conventional GTG-banding along with molecular cytogenetic techniques is useful in detecting genomic alterations and rearrangements. Comprehensive characterization of chromosomal rearrangements like sSMC has the potential to save potentially healthy fetuses from being terminated.
MASKED INV DUP(22)(Q11.23), TETRASOMY 8 AND TRISOMY 19 IN A BLAST CRISIS-CHRONIC MYELOID LEUKEMIA AFTER INTERRUPTED IMA-TINIB-TREATMENT
Wafa A.1, Almedani S.1, Moassass F.1, Liehr T.2, Othman M.A.K.2, Al-Achkar W.1
'Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, Damascus, Syria
Jena University Hospital, Institute of Human Genetics, Jena, Germany
The Philadelphia (Ph) chromosome, or derivative chromosome 22 [der(22)], is product of the reciprocal translocation t(9;22). It is the hallmark of chronic myelogenous leukemia (CML). It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 to the 3' part of the ABL1 gene on chromosome 9. During CML progression 60-80% of the cases acquire additional genetic changes. Blast crisis (BC) is characterized by the rapid expansion of a population of differentiation arrested blast cells (myeloid or lymphoid cells population), often presenting with secondary chromosomal abnormalities. Here we report a new CML-BC case with a derivative chromosome 22 inv dup(22)(qll.23) associated with tetrasomy 8 and trisomy 19. These chromosomal aberrations were observed after the patient stopped IM treatment for overall 16 months.A complete cytoge-netic and molecular cytogenetic analysis was performed and application of molecular genetic methods such as reverse transcription polymerase chain reaction (RT-PCR) finally characterized a complex karyotype including an inv dup(22)(q11.23), a del(9)(p24p12) tetrasomy 8 and trisomy 19. Obviously BC resulted in the present patient after to IM treatment was interrupted. The underlying mechanisms and prognostic implications of these cytogenetic abnormalities are discussed. This work was supported by the AECS, in parts by the DAAD.
INTERSTITIAL DELETION 9P23 TO 9P11.1 AS SOLE ADDITIONAL ABNORMALITY IN A PHILADELPHIA POSITIVE CHRONIC MYELOID LEUKEMIA IN BLAST CRISIS: A RARE EVENT
Wafa A.1, Asa'adM.1, Ikhtiar A.2, Liehr T.3, Al-Achkar W.1
1Human Genetics Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, Damascus, Syria
2Mammalians Biology Division, Department of Molecular Biology and Biotechnology, Atomic Energy Commission, Damascus, Syria
Jena University Hospital, Institute of Human Genetics, Jena, Germany
РОССИЙСКИЙ ВЕСТНИКПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 4, 2015
