RESUMO
Rett syndrome is an X-linked dominant neurodevelopmental disorder that affects females almost exclusively. The recent identification of mutations of the methyl-CpG-binding protein 2 gene (MECP2) in patients with RTT, encouraged us to analyze the gene in 37 Japanese patients divided into classical RTT (14 cases), variant RTT (13 cases), and mentally retarded patients with Rett-like features (10 cases). Mutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases). Six reported common mutations were detected in 17 cases, and rare single nucleotide substitutions were found in 3 patients. In addition, one insertion mutation (1189insA) and four deletion mutations including one double deletion mutant (451delG, 100del4, 1124del53 and 881del289 plus 1187del8) were newly identified. In the 10 mentally retarded patients with Rett-like features, however, no mutation was detected in the coding region of MECP2. The finding of MECP2 mutations in 92.5% of patients with RTT indicates that RTT fulfilling the diagnostic criteria are due to genetic alteration.
Assuntos
Proteínas Cromossômicas não Histona , Proteínas de Ligação a DNA/genética , Proteínas Repressoras , Síndrome de Rett/genética , Substituição de Aminoácidos , DNA/química , DNA/genética , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Japão , Masculino , Proteína 2 de Ligação a Metil-CpG , Mutagênese Insercional , Mutação , Fenótipo , Mutação Puntual , Síndrome de Rett/patologia , Deleção de SequênciaRESUMO
Chromosome 14q +, which represents a chromosomal rearrangement involving the immunoglobulin heavy chain gene (IgH) locus, is a genetic hallmark of human multiple myeloma (MM). Here, we report the identification of (14;20)(q32;q11) chromosomal translocations found in MM cells. Double color fluorescence in situ hybridization analyses pinpointed the breakpoints at the 20q11 locus in two MM cell lines within a length of at most 680 kb between the KIAA0823 and MAFB gene loci. Among the transcribed sequences in the vicinity of the breakpoints, an ectopic expression of the MAFB gene, which is located at 450 - 680 kb telomeric to one of the breakpoints and encodes a member of the MAF family basic region / leucine zipper transcription factor, was demonstrated to be associated with t(14;20). This finding, together with that of a previous study describing its transforming activity, suggests that the MAFB gene may be one of the targets deregulated by regulatory elements of the IgH gene as a result of t(14;20).
Assuntos
Proteínas Aviárias , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 20 , Proteínas de Ligação a DNA , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Proteínas Oncogênicas/biossíntese , Transativadores/biossíntese , Fatores de Transcrição , Translocação Genética , Northern Blotting , Cromossomos Artificiais de Levedura , Elementos Facilitadores Genéticos , Genes de Imunoglobulinas/genética , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Fator de Transcrição MafB , Modelos Genéticos , Fenótipo , RNA Mensageiro/metabolismo , Sitios de Sequências Rotuladas , Células Tumorais CultivadasRESUMO
The chromosomes of a cell line (NALM-1) derived from the leukocytes of a patient with chronic myelocytic leukemia (CML) were examined with several banding techniques. The modal chromosome number was 46 and the cells contained a Philadelphia chromosome (Ph1), due to the standard translocation of the missing segment of the long arm of chromosome No. 22 onto the distal end of the long arm of chromosome No. 9, i.e., t(9;22) (q34;q11). The Ph1-positive modal cells of the NALM-1 line also had two common marker chromosomes, an extra X-chromosome, and missing chromosomes in groups No. 7, 9, and 15. Immunologic examination of the NALM-1 cells revealed them to have non-T-non-B (null) surface characteristics. An antigen specific for cells of acute leukemia and a human la-like antigen were detected. These facts suggested that the NALM-1 cell line originated from CML cells and maintained the cytogenetic and Immunologic characteristics of such cells.
Assuntos
Linhagem Celular , Cromossomos Humanos 21-22 e Y , Leucemia Mieloide/genética , Animais , Antígenos de Neoplasias , Linfócitos B/imunologia , Cromossomos Humanos 13-15 , Cromossomos Humanos 6-12 e X , Antígenos HLA , Humanos , Leucemia Experimental/genética , Leucemia Experimental/imunologia , Leucemia Linfoide/imunologia , Leucócitos/imunologia , Cromossomos Sexuais , Linfócitos T/imunologia , Translocação GenéticaRESUMO
Comparison of the chromosome findings obtained on routine examination (10-50 cells) of the marrows from patients with Ph1-positive CML with those based on a large number (110-500 cells) of metaphases in six of these patients, in whom appropriate material was available, revealed the presence of small percentages of aneuploid cells in the marrow during the chronic phase of the disease and not seen with the routine procedure. These aneuploid cells may ultimately constitute the dominant clone during the blastic phase of the chronic myelocytic leukemia (CML). Furthermore, karyotypically abnormal cells, in addition those observed on routine study, were detected in the blastic phase when a large number of cells was examined. The value and implications of these observations are discussed.
