RESUMO
Congenital Complex Chromosome rearrangements (CCRs) compatible with life are rare in humans. We report a de novo CCR involving chromosomes 8, 11 and 16 with 4 breakpoints in a patient with mild dysmorphic features, acquisition delay and psychotic disorder. Conventional cytogenetic analysis revealed an apparently balanced 8;16 translocation. Further FISH analysis with WCP 8 and WCP 16 probes revealed the presence of a third chromosome involved in the translocation. The multicolour karyotype confirmed the complexity of the rearrangement and showed that the derivative chromosome 8 was composed of 3 distinct segments derived from chromosomes 8, 16 and 11. The breakpoints of this complex rearrangement were located at 8q21, 11q14, 11q23 and 16q12. Comparative genomic hybridization (CGH) and array-CGH were performed to investigate the possibility of any genomic imbalance as a result of the complex rearrangement. No imbalance was detected by these two techniques. Our study showed: i) the necessity to confirm reciprocal translocations with FISH using painting probes, particularly when the karyotype resolution is weak; ii) the usefulness of multicolour karyotype for the characterization of structural chromosomal rearrangements, particularly when they are complex; iii) the usefulness of CGH and array-CGH in cases of abnormal phenotype and apparently balanced rearrangement in order to explore the breakpoints and to detect additional imbalances.
Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 8/genética , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/genética , Transtornos Psicóticos/complicações , Transtornos Psicóticos/genética , Criança , Aberrações Cromossômicas , Deficiências do Desenvolvimento/diagnóstico , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Hibridização de Ácido Nucleico , Fenótipo , Transtornos Psicóticos/diagnósticoRESUMO
Heterochromatin confined to pericentromeric and secondary constriction regions plays a major role in morphological variation of chromosome 9, because of its size and affinity for pericentric inversion. We report on a 6-year-old boy with growth and language delay, minor facial anomalies and unusual chromosome 9 variant with an extra-band in the centromeric region on the conventional karyotype. Subsequent analysis by FISH and CGH identified this variant as a dicentric chromosome 9 with a duplication of the 9p12-q21 region. An identical chromosome 9 variant was found in the mild language retarded brother and in the phenotypically normal father and grandfather. The presumed mechanism accounting for the phenotypic discordance observed in this family and the usefulness of CGH in characterization of such variants are discussed. To our knowledge, this is the first investigation of an unusual chromosome 9 variant by CGH.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 9 , Variação Genética , Criança , Face/anormalidades , Feminino , Transtornos do Crescimento/genética , Humanos , Hibridização in Situ Fluorescente , Transtornos da Linguagem/genética , Masculino , Linhagem , FenótipoRESUMO
We conducted a review of cancers in Down syndrome (DS), because solid tumors are poorly understood in DS. Cancers are in excess in this condition because of the 20-fold excess of leukemias, whereas malignant solid tumors seem to be globally underrepresented as compared with those in the general population. However, among these tumors, some tumors are in excess: lymphomas, gonadal and extragonadal germ cell tumors, and possibly retinoblastomas and pancreatic and bone tumors. Neoplasms in excess are seen earlier, sometimes in fetal life (leukemias and testicular germ cell tumors) or neonatally (leukemias and lymphoma) and affect mainly male subjects. There seems to exist an excess of rare karyotypes. Other tumors are underrepresented, particularly neuroblastomas and nephroblastomas, in young children, and perhaps common epithelial tumors in adults. These observations suggest that DS has a particular tumor profile, with some tissues more affected by malignant diseases (hematopoietic tissue and germ cells) and others that seem to be protected (central and peripheral nervous system, renal tissue, and epithelial tissues). The mechanism is mainly genetic, but differences in exposure to exogenous agents compared with the general population must be kept in mind. These findings are of interest for the management of these patients and early detection of cancers. Better knowledge of this tumor profile could help us to understand the mechanisms of carcinogenesis and should be compared to the current knowledge of genes on chromosome 21.
Assuntos
Síndrome de Down/complicações , Neoplasias/complicações , Adulto , Idade de Início , Criança , Síndrome de Down/epidemiologia , Síndrome de Down/genética , Feminino , Humanos , Recém-Nascido , Leucemia/complicações , Leucemia/epidemiologia , Leucemia/genética , Masculino , Neoplasias/congênito , Neoplasias/epidemiologia , Neoplasias/genética , Razão de MasculinidadeRESUMO
A patient with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia is described who also developed an abnormality of chromosome #3, i.e., t(3;20)(p21;p13), in blast crisis. This abnormality may be connected with the advent thrombocythemia. The disease was a thrombopenia in the initial phase.
Assuntos
Cromossomos Humanos 1-3 , Cromossomos Humanos 19-20 , Leucemia Mieloide/genética , Cromossomo Filadélfia , Trombocitose/genética , Translocação Genética , Adulto , Humanos , MasculinoRESUMO
A case of chronic myelogenous leukemia (CML) in a young woman with a new variant Ph1-translocation--i.e., t(8;22) (q24;q12)--is described. The clinical and biological aspects of the disease did not seem to differ from those of the usual cases of CML.
Assuntos
Aberrações Cromossômicas/genética , Cromossomos Humanos 21-22 e Y , Cromossomos Humanos 6-12 e X , Leucemia Mieloide/genética , Adulto , Bandeamento Cromossômico , Transtornos Cromossômicos , Feminino , Humanos , Leucemia Mieloide/tratamento farmacológico , Translocação GenéticaRESUMO
The authors describe cytogenetic aberrations observed in a case of T prolymphocytic leukemia. C11 deletion (q14) B5 deletion (pter), D14q +, E20 trisomy, and two markers are the main anomalies of the complement.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos 6-12 e X , Leucemia Linfoide/genética , Idoso , Medula Óssea/fisiopatologia , Células Cultivadas , Bandeamento Cromossômico , Deleção Cromossômica , Humanos , Cariotipagem , Masculino , Linfócitos T/fisiologia , TrissomiaRESUMO
Dealing with a routine regional cytogenetic activity, we have developed and adapted to clinical work a semi automatic karyotyping machine. Attempts for an accurate automated chromosome classification using a neural network have led to partial results. A specific adaptation to cancer cytogenetics is under development (determination of the modal number, translocations analysis with densitometric curves, automatic identification of markers). A specific program allows quantification of chromosome labelling with radioactive probes. Exchanges of digitized karyotypes are feasible with labs using automated karyotyping machines. A local network connects several karyotyping and metaphase finding stations. Guidelines for an international data bank concerning abnormal chromosome images have been elaborated. On the other hand the ISH techniques have been applied to the following topics: identification of human chromosome aberrations in amniotic and chorionic cells, chromosome studies of human gametes and embryos (including sex determination), identification of markers in cancer cells.
Assuntos
Aberrações Cromossômicas , Cromossomos , Processamento de Imagem Assistida por Computador/métodos , Cariotipagem/métodos , Neoplasias/genética , Classificação/métodos , Humanos , Cariotipagem/instrumentaçãoRESUMO
We describe a case of left cervical stage I centroblastic lymphoma in a 29-year old male patient with Down's syndrome due to a (14; 21) Robertsonian translocation. The disease presented as extensive lymph node necrosis leaving rare areas of tumor cells, accounting for the diagnostic difficulties. According to our review of the literature, lymphoma is one of the most common neoplasms in DS patients and may represent the second most common malignancy in this condition, far behind leukemia.
Assuntos
Síndrome de Down/complicações , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico , Adulto , Síndrome de Down/genética , Evolução Fatal , Humanos , Linfonodos/patologia , Linfoma de Células B/patologia , Masculino , Translocação GenéticaRESUMO
During a gestation with oligoamnios and growth retardation noticed at 25th week an amniocentesis allowed us to discover the 14th case of complete trisomy 9, the third detected in utero. It is also the first without heart malformation, otherwise phenotype was usual. The liver had small areas of necrosis with calcifications and slight fibrosis which may be in relation with two cordocentesis made before expulsion. The important phenotype alterations and poor outcome of fetuses with trisomy 9 justify elective abortion.
Assuntos
Amniocentese/métodos , Cromossomos Humanos Par 9 , Retardo do Crescimento Fetal/diagnóstico , Oligo-Hidrâmnio/diagnóstico , Diagnóstico Pré-Natal/métodos , Trissomia , Aborto Terapêutico , Adulto , Feminino , Retardo do Crescimento Fetal/complicações , Retardo do Crescimento Fetal/etiologia , Humanos , Recém-Nascido , Cariotipagem , Hepatopatias/complicações , Hepatopatias/congênito , Hepatopatias/patologia , Masculino , Oligo-Hidrâmnio/etiologia , FenótipoAssuntos
Animais Recém-Nascidos , Epitélio/ultraestrutura , Gengiva/ultraestrutura , Junções Intercelulares/ultraestrutura , Animais , Membrana Basal/ultraestrutura , Gatos , Membrana Celular/ultraestrutura , Núcleo Celular/ultraestrutura , Tecido Conjuntivo/ultraestrutura , Células do Tecido Conjuntivo , Grânulos Citoplasmáticos/ultraestrutura , Desmossomos/ultraestrutura , Feminino , Hialina , Queratinas , Masculino , Microscopia Eletrônica , Odontogênese , Erupção Dentária , Vacúolos/ultraestruturaRESUMO
The authors observed in electronic microscopy the methyl-bis-beta chlorethylamine action (nitrogen mustard) on normal human chromosomes. The effects were obtained in vitro after colchicine blocking and on grids after fixation. The action is remarkable on the fiber and on the chromatid's structure.
Assuntos
Cromossomos/efeitos dos fármacos , Mecloretamina/farmacologia , Células Cultivadas , Cromátides/ultraestrutura , Cromossomos/ultraestrutura , Humanos , Linfócitos/ultraestruturaRESUMO
Ultrastructural studies of cultured skin fibroblasts derived from an individual affected with Tay-Sachs disease (GM2 gangliosidosis variant B) diagnosed by clinical observation and hexosaminidase A deficiency, revealed several lamellar lysosomal inclusions. These inclusions are not seen in cultured fibroblasts and cultured amniotic fluid cells derived from individuals heterozygotic for Tay-Sachs disease. Normal cells were cultured and observed for comparison.