RESUMO
Inverted duplications with terminal deletions are a well-defined family of complex rearrangements already observed for most of chromosome extremities. Several mechanisms have been suggested which could lead to their occurrence, either through non-homologous end joining, non-allelic homologous recombination, or more recently through an intrastrand fold-back mechanism. We describe here a patient with intellectual disability and pharmacoresistant epilepsy, for which array CGH analysis showed the first interstitial case of inverted duplication with deletion on chromosome 1p. Furthermore, SNP array analysis revealed an associated segmental isodisomy for the distal part of 1p, which led us to consider a replicative mechanism to explain this abnormality. This observation extends the range of this once telomeric rearrangement.
Assuntos
Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Aberrações Cromossômicas , Cromossomos Humanos Par 1/genética , Epilepsia/patologia , Deficiência Intelectual/patologia , Adulto , Hibridização Genômica Comparativa , Epilepsia/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/genética , Cariotipagem , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
ICF (immunodeficiency, centromeric region instability, facial anomalies) syndrome is a rare autosomal recessive disorder characterised by severe immunodeficiency, craniofacial anomalies and chromosome instability. Chromosome analyses from blood samples show a high frequency of decondensation of pericentromeric heterochromatin (PH) and rearrangements involving chromosomes 1 and 16. It is the first and, as far as we know, the only disease associated with a mutation in a DNA methyltransferase gene, DNMT3B, with significant hypomethylation of the classical satellite DNA, the major component of the juxtacentromeric heterochromatin. To better understand the complex links between the hypomethylation of the satellite DNA, the cytogenetic anomalies and the clinical features of ICF syndrome, we performed three-dimensional (3D) FISH on preserved cells from a patient with a suspected ICF phenotype. Analysis of DNMT3B did not reveal any mutation in our patient, making this case an ICF type 2. The results of 3D-FISH showed a statistically significant change in the intranuclear position of PH of chromosome 1 in cells of the patient as compared to normal cells. It is difficult to understand how a defect in the methylation pathway can be responsible for the various symptoms of this condition. From our observations we suggest a mechanistic link between the reorganisation of the nuclear architecture and the altered gene expression.
Assuntos
Núcleo Celular/genética , Centrômero , Heterocromatina/química , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Adolescente , Aberrações Cromossômicas , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 9 , Metilação de DNA , DNA Satélite , Face/anormalidades , Feminino , Humanos , Hibridização in Situ Fluorescente , Doenças da Imunodeficiência PrimáriaRESUMO
Male phenotype associated with a 45,X karyotype is an infrequent finding. We present a case diagnosed prenatally on amniocentesis performed for maternal age. The male phenotype was associated with a translocation of a distal part of Yp including the pseudoautosomal SHOX gene and SRY gene on the short arm of a chromosome 21. By DNA analysis we could show that the X chromosome was of maternal origin and that the breakpoint was in interval 3 of the Y chromosome. Mechanisms and genetic counselling are discussed based on a review of published cases of 45,X and XX males.
Assuntos
Amniocentese , Cromossomos Humanos Par 21 , Cromossomos Humanos Y , Proteínas de Ligação a DNA/genética , Proteínas Nucleares , Aberrações dos Cromossomos Sexuais , Fatores de Transcrição , Translocação Genética , Adulto , Quebra Cromossômica , Cromossomos Humanos X , Feminino , Deleção de Genes , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Idade Materna , Fenótipo , Gravidez , Gravidez de Alto Risco , Proteína da Região Y Determinante do SexoRESUMO
Parental-specific epigenetic modifications are imprinted on a subset of genes in the mammalian genome during germ cell maturation. However, the precise timing of their establishment remains to be determined. Methylation of CpG dinucleotides has been shown to be a part of the parental imprint. We have examined how the methylation pattern characteristic of the paternal allele in germ cells are established during human spermatogenesis. Two representative imprinted genes, H19 and MEST/PEG1, were studied. The experiments were performed using the bisulphite sequencing method on microdissected individual cells at different stages of male germ cell differentiation. We show that both genes are unmethylated in fetal spermatogonia, suggesting that all pre-existing methylation imprints are already erased by this stage. The MEST/PEG1 gene remains unmethylated at all subsequent post-pubertal stages of spermatogenesis, including mature spermatozoa. The methylation of H19 typical of the paternal allele first appears in a subset of adult spermatogonia and then is maintained in spermatocytes, spermatids and mature spermatozoa. Our results suggest that the methylation imprint inherited from the parents is first erased in the male germ line at an early fetal stage. The paternal-specific imprint is re-established only later, during spermatogonial differentiation in the adult testis.
Assuntos
Metilação de DNA , Impressão Genômica , Proteínas/genética , RNA não Traduzido/genética , Espermatozoides/fisiologia , Adulto , Fatores Etários , Diferenciação Celular , Clonagem Molecular , Ilhas de CpG , Pai , Humanos , Masculino , Modelos Genéticos , Dados de Sequência Molecular , RNA Longo não Codificante , Sefarose/metabolismo , Espermatócitos/citologia , Espermatócitos/metabolismo , Espermatogônias/citologia , Espermatogônias/metabolismo , Espermatozoides/citologia , Espermatozoides/crescimento & desenvolvimento , Espermatozoides/metabolismo , Sulfitos/metabolismo , Fatores de TempoAssuntos
Aberrações Cromossômicas , Células-Tronco Hematopoéticas/patologia , Síndromes Mielodisplásicas/genética , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária com Excesso de Blastos/genética , Anemia Refratária com Excesso de Blastos/patologia , Técnicas de Cultura de Células/métodos , Células Cultivadas , Colágeno , Feminino , Humanos , Hibridização in Situ Fluorescente , Interfase , Cariotipagem , Masculino , Síndromes Mielodisplásicas/patologiaAssuntos
Síndrome de Angelman , Cromossomos Humanos Par 15 , Síndrome de Prader-Willi , Aneuploidia , Síndrome de Angelman/complicações , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/genética , Pré-Escolar , Feminino , Impressão Genômica , Humanos , Repetições de Microssatélites , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genéticaRESUMO
Myelodysplastic syndromes (MDS) are clonal malignancies characterized by peripheral blood pancytopenia and signs of maturation disturbances of one or several cell lineages in bone marrow. MDS present as chimeras associating normal polyclonal and malignant monoclonal progenitors cells in various proportions. Numerous cytogenetic abnormalities have been reported in MDS and can be detected by fluorescence in situ hybridization (FISH) on interphase cells. We have used this technique on methylcellulose cultured hematopoietic progenitors obtained from three patients suffering from MDS and exhibiting informative karyotypic features. Hematopoietic cells were cultured for 14 days, and individual clones (BFU-E, CFU-GM) were picked up and then cytocentrifuged for FISH analysis. We used centromeric probes realized and labeled in our laboratory by PCR to detect aneuploidies for chromosomes 7 and 11 in two patients. Furthermore, we could detect a 5q partial deletion on interphase cells from the third patient using a 5q31 specific probe visualized with the HNPP Fluorescent Detection Set from Boehringer Mannheim. In conclusion, FISH is a helpful method to detect malignant clones in hematopoietic progenitor cultures and hence to study the relative growth of normal vs. leukemic cells in MDS.
Assuntos
Células-Tronco Hematopoéticas/patologia , Hibridização in Situ Fluorescente/métodos , Síndromes Mielodisplásicas/diagnóstico , Idoso , Aneuploidia , Células Cultivadas , Centrômero , Aberrações Cromossômicas/diagnóstico , Transtornos Cromossômicos , Feminino , Humanos , Masculino , Metilcelulose , Pessoa de Meia-IdadeRESUMO
We describe a new case of mosaic isochromosome 20q revealed by amniocentesis. A 46,XX/46,XX,i(20q) chromosomic complement was indirectly confirmed by fluorescent in situ hybridization. Since control chromosome analysis performed on cord blood showed a normal karyotype, pregnancy was continued and resulted in the birth of a normal female infant.