RESUMO
OBJECTIVE: Array comparative genomic hybridization (CGH) is transforming clinical cytogenetics with its ability to interrogate the human genome at increasingly high resolution. The aim of this study was to determine whether array CGH testing in the prenatal population provides diagnostic information over conventional karyotyping. METHODS: MEDLINE (1970 to December 2009), EMBASE (1980 to December 2009) and CINAHL (1982 to December 2009) databases were searched electronically. Studies were selected if array CGH was used on prenatal samples or if array CGH was used on postnatal samples following termination of pregnancy for structural abnormalities that were detected on an ultrasound scan. Of the 135 potential articles, 10 were included in this systematic review and eight were included in the meta-analysis. The pooled rate of extra information detected by array CGH when the prenatal karyotype was normal was meta-analyzed using a random-effects model. The pooled rate of receiving an array CGH result of unknown significance was also meta-analyzed. RESULTS: Array CGH detected 3.6% (95% CI, 1.5-8.5) additional genomic imbalances when conventional karyo-typing was 'normal', regardless of referral indication. This increased to 5.2% (95% CI, 1.9-13.9) more than karyotyping when the referral indication was a structural malformation on ultrasound. CONCLUSIONS: There appears to be an increased detection rate of chromosomal imbalances, compared with conventional karyotyping, when array CGH techniques are employed in the prenatal population. However, some are copy number imbalances that are not clinically significant. This carries implications for prenatal counseling and maternal anxiety.
Assuntos
Transtornos Cromossômicos/diagnóstico , Hibridização Genômica Comparativa/métodos , Cariotipagem/métodos , Aberrações Cromossômicas , Transtornos Cromossômicos/genética , Feminino , Genoma Humano , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Gravidez , Diagnóstico Pré-NatalRESUMO
One case of de novo Ph-negative T-cell acute lymphoblastic leukaemia has been found to have a classical breakpoint cluster region (bcr) rearrangement of the type seen in chronic granulocytic leukaemia. There were no haematological features to suggest a previous chronic phase. This case represents the first report of this rearrangement in Ph negative acute T-lymphoblastic leukaemia at presentation. The implications for various therapeutic options in such patients are discussed.
Assuntos
Rearranjo Gênico , Leucemia-Linfoma de Células T do Adulto/genética , Família Multigênica , Oncogenes , Cromossomo Filadélfia , Adulto , Southern Blotting , Cromossomos Humanos Par 22 , Humanos , MasculinoRESUMO
Granulocytic sarcoma is a rare complication of leukaemia. Occasionally it presents before the development of systemic leukaemia when diagnosis may be difficult. A case of granulocytic sarcoma occurring in a patient with no overt evidence of leukaemia, but in whom cytogenetic analysis of the bone marrow showed a clonal t(12;13) translocation, is reported. Cytogenetic analysis of tissues in this disease may indicate evidence of systemic disease before overt morphological changes.
Assuntos
Medula Óssea/patologia , Leucemia Mieloide/genética , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Translocação GenéticaRESUMO
A child with disseminated Ewing's sarcoma underwent cytogenetic investigations which showed different structural rearrangements of chromosome 22 at diagnosis (?ring22), and at relapse [t(10;22)], but the classic translocation t(11;22) was not detectable. This case provides further evidence of the importance of chromosome 22 in this disease, while raising some questions about the central importance of the translocation between chromosomes 11 and 22.
Assuntos
Aberrações Cromossômicas/complicações , Cromossomos Humanos Par 22 , Sarcoma de Ewing/genética , Neoplasias Ósseas/complicações , Neoplasias Ósseas/genética , Criança , Transtornos Cromossômicos , Cromossomos Humanos Par 11 , Feminino , Humanos , Ílio , Cariotipagem , Sarcoma de Ewing/complicações , Translocação GenéticaRESUMO
In a patient with stage IV disseminated neuroblastoma treated by chemotherapy extensive cytogenetic investigations were performed on the residual primary tumour and bone marrow immediately before myeloablative treatment and autologous marrow rescue. Two abnormal clones both showing lp+, a characteristic abnormality of neuroblastoma, were detected in cells from the residual primary tumour, providing direct evidence of persisting viable tumour. Such investigations should be a routine part of the assessment of response to treatment in patients with neuroblastoma, and could be extended to others in whom "second look" surgery is performed.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Medula Óssea/ultraestrutura , Neuroblastoma/genética , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/ultraestrutura , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sobrevivência Celular , Criança , Humanos , Cariotipagem , Masculino , Neuroblastoma/tratamento farmacológico , Neuroblastoma/ultraestrutura , Translocação GenéticaRESUMO
A case of t(9;11)(p22;q24) in a patient with acute monocytic leukemia is described. The difficulties of establishing the precise breakpoints involved in this emerging association are discussed.
Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 9 , Leucemia Monocítica Aguda/genética , Translocação Genética , Adulto , Medula Óssea/patologia , Humanos , Cariotipagem , MasculinoRESUMO
Two distinct karyotypically abnormal cell lines were observed in cultures of a primitive neuroectodermal tumor. One involved multiple chromosome rearrangements, and the other an inversion of chromosome #7 and a t(3;10) showing an interstitial deletion of 3p; del(3)(p1?4p1?2). None of these rearrangements have been reported in previous descriptions of primitive neuroectodermal tumor karyotypes.
Assuntos
Aberrações Cromossômicas , Neoplasias Maxilares/genética , Neoplasias Embrionárias de Células Germinativas/genética , Criança , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 3 , Cromossomos Humanos Par 7 , Marcadores Genéticos , Humanos , Cariotipagem , Masculino , Translocação GenéticaRESUMO
A 16-year-old boy with leukemia had a marked leucocytosis (165 x 10(9)/L) at presentation. The large number of neutrophils, myelocytes, and metamyelocytes and negative leucocyte alkaline phosphatase reaction raised the possibility of chronic myeloid leukemia. Cytogenetic analysis showed a deletion of chromosome 7, a t (8;21), a missing Y chromosome, and, in some cells, duplication of the der(21). The Philadelphia chromosome was not detected, nor was the breakpoint cluster region of chromosome 22 found to be rearranged. Myeloid leukemia with t (8;21) can therefore be associated with a greater degree of granulocytic hyperplasia than has so far been apparent, and cytogenetic analysis in this case has been crucial in distinguishing leukemia types.
Assuntos
Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Granulócitos/patologia , Leucemia Mieloide/genética , Translocação Genética , Adolescente , Diagnóstico Diferencial , Humanos , Hiperplasia , Cariotipagem , Leucemia Mieloide/patologia , MasculinoRESUMO
Recent reports have indicated that monosomy 3 is a marker of poor prognosis in uveal melanoma. Fluorescence in situ hybridization (FISH) was performed on fresh touch preparations from 17 uveal, and 5 conjunctival melanomas, using the chromosome 3 centromeric probe, D3Z1. Of the 17 uveal melanomas, all of which originated in the choroid, two cases revealed a monosomy of chromosome 3. One of the conjunctival melanomas contained a major clone that was trisomic for chromosome 3, and another conjunctival melanoma contained a tetrasomic population. FISH, using the alpha-satellite probe for chromosome 3 on uveal melanoma imprints, allows one to predict which patients are potentially at a higher risk of relapse. Multiplication, rather than deletion, of copies of chromosome 3 in conjunctival melanomas may be a nonspecific aberration, perhaps indicative of polyploidy, a characteristic of tumor progression.
Assuntos
Neoplasias da Coroide/genética , Cromossomos Humanos Par 3 , Neoplasias da Túnica Conjuntiva/genética , Melanoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Coroide/patologia , Neoplasias da Túnica Conjuntiva/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Melanoma/patologia , Pessoa de Meia-IdadeRESUMO
Congenital (infantile) fibrosarcoma is a rare soft tissue sarcoma occurring in children aged less than 5 years. We performed cytogenetic analysis on such a tumor, which had an abnormal karyotype: 48,XY, +11, +20. Three other reports of karyotypes in congenital fibrosarcoma describe similar cytogenetic changes, and a specific pattern of trisomies that may prove diagnostic for this tumor is beginning to emerge.
Assuntos
Fibrossarcoma/congênito , Fibrossarcoma/genética , Perna (Membro) , Neoplasias de Tecidos Moles/congênito , Neoplasias de Tecidos Moles/genética , Humanos , Recém-Nascido , Cariotipagem , MasculinoRESUMO
Multiple karyotypically abnormal cell lines were observed in long-term cultures of an ependymoma of the fourth ventricle of a child. A previous report of a G-banded ependymoma karyotype described monosomy 8, trisomy 9, t(1;7)(p12;p13), and t(X;10)(q22-23;q24). This case also shows involvement of Xq22 and 10q24.
Assuntos
Neoplasias do Ventrículo Cerebral/genética , Aberrações Cromossômicas , Ependimoma/genética , Neoplasias do Ventrículo Cerebral/patologia , Pré-Escolar , Ependimoma/patologia , Marcadores Genéticos , Humanos , Cariotipagem , MasculinoRESUMO
OBJECTIVES: QF-PCR analysis can be used as a rapid test to diagnose primary trisomy in prenatal samples. Mosaicism in CVS detected by QF-PCR has previously been reported; however, no case has so far been reported in which the QF-PCR result was completely discrepant to that of the karyotype analysis from a long-term culture. METHODS: A CVS, referred because of a high serum screening risk of 1:10 for Down Syndrome and 1:110 for Edwards Syndrome, was tested by QF-PCR analysis and chromosome analysis of cultured cells. Subsequent analyses were carried out on a follow-up amniotic fluid sample and foetal tissue samples. RESULTS: Conflicting results were obtained between QF-PCR analysis on two independent fronds from the chorionic villi and chromosome analysis on cultured CVS. Cytogenetic and molecular analysis on a subsequent amniotic fluid sample indicated trisomy 18 with no evidence of mosaicism. Analysis of follow-up tissue confirmed trisomy in a foetal skin sample and mosaicism for trisomy 18 in four placental sites tested. CONCLUSION: We report here an apparently normal CVS QF-PCR result that was completely discrepant with the trisomy 18 positive karyotype result on long-term culture. This has important implications regarding our current testing protocol.
Assuntos
Amostra da Vilosidade Coriônica/métodos , Transtornos Cromossômicos/diagnóstico , Cariotipagem/métodos , Reação em Cadeia da Polimerase/métodos , Trissomia , Adulto , Técnicas de Cultura de Células , Cromossomos Humanos Par 18 , Feminino , Humanos , Hibridização in Situ Fluorescente , Gravidez , Pele/patologiaRESUMO
Although trisomy 16 is well recognised in spontaneous abortuses, it is infrequent in livebirths and there is little information about the clinical effects. We report two sibs with partial trisomy 16q resulting in infant death. Both children were severely growth retarded with small elfin faces, prominent foreheads, low set ears, abnormal external genitalia, and intractable diarrhoea.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos 16-18 , Cromossomos Humanos 19-20 , Feminino , Humanos , Recém-Nascido , Linhagem , Translocação Genética , TrissomiaRESUMO
In a retrospective collaborative study involving 21 U.K. laboratories and 11,775 CVS prenatal diagnostic procedures, a total of 73 cases of confined placental mosaicism (CPM) were identified among the 8004 first-trimester referrals because of advanced maternal age, a previous child with a numerical chromosome abnormality, or a family history of the same. Data were collected on subsequent cytogenetic follow-up and pregnancy outcome for each case and a referral matched control. Comparison with the control population failed to demonstrate a marked increase in adverse pregnancy outcome in the CPM group, but a significant increase in both low and high birth weight infants was recorded. In a parallel study, 7 out of 108 cases, referred for prenatal diagnosis because of ultrasound detection of isolated intrauterine growth retardation (IUGR) in the second or third trimester, were shown to have a chromosome abnormality restricted to the extraembryonic tissues. These included cases of CPM involving trisomy 9 and del(13)(q13), neither of which has previously been reported in association with IUGR.
Assuntos
Aberrações Cromossômicas , Retardo do Crescimento Fetal/genética , Mosaicismo , Placenta , Resultado da Gravidez , Adulto , Peso ao Nascer , Feminino , Deleção de Genes , Humanos , Masculino , Idade Materna , Gravidez , Gravidez de Alto Risco , Estudos Retrospectivos , Trissomia , Ultrassonografia Pré-Natal , Reino UnidoRESUMO
A translocation of material from chromosome 11 to chromosome 14 was identified in a 7-month-old male with microcephaly and developmental delay. The break-points appear to be on the long arm of chromosome 11, close to the centromere, and on the short arm of the 14.
Assuntos
Cromossomos Humanos 13-15 , Cromossomos Humanos 6-12 e X , Microcefalia/genética , Transtornos Psicomotores/genética , Translocação Genética , Humanos , Lactente , Masculino , FenótipoRESUMO
In three families in the North of England, where retinoblastoma is transmitted, 41 members were studied by high resolution chromosome banding at the 500+ and 900+ levels. None of the 10 affected individuals or their normal relatives showed any deletion in the 13q14 region.
Assuntos
Cromossomos Humanos Par 13 , Retinoblastoma/genética , Bandeamento Cromossômico , Deleção Cromossômica , Humanos , LinhagemRESUMO
Recombination of an inherited pericentric inversion of chromosome 20 has given rise to a child with partial trisomy 20p. To our knowledge no previous familial inversions of this chromosome have been described in the literature.
Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 20 , Troca Genética , Trissomia , Bandeamento Cromossômico , Humanos , Lactente , Masculino , LinhagemRESUMO
A case of Prader Willi Syndrome who suffered from hypothyroidism is described. This patient on cytogenetic examination was found to have Mosaic 46,XX/46,XX,del(15)(q11.1q11.2) karyotype.
Assuntos
Hipotireoidismo/genética , Síndrome de Prader-Willi/genética , Adulto , Desenvolvimento Infantil , Deleção Cromossômica , Cromossomos Humanos Par 15 , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , Obesidade/genéticaRESUMO
Two brothers developed hypoplastic anaemia with the development in one of refractory anaemia with excess blasts (RAEB) accompanied by emergence of monosomy 7. Both brothers have a constitutional inversion of chromosome 1. Neither shows the increased chromosomal fragility of Fanconi's anaemia or its variants. This family is the third reported in which monosomy 7 has been found when leukaemic or preleukaemic transformation has occurred in patients with familial hypoplastic anaemia.