RESUMEN
Pallister-Killian syndrome is a clinically recognizable syndrome characterized by tissue-limited mosaicism for an extra 12p isochromosome. Very little is known about the underlying mechanism of this rare rearrangement. Microsatellite markers were studied from three fetuses with Pallister-Killian syndrome and their parents to determine the parent of origin and the cell division yielding the additional isochromosome. In two cases the isochromosome contained the same allele(s) as a normal transmitted chromosome 12, one paternal and one maternal in origin. A third case showed inheritance of two different maternal alleles, indicating that at least one meiotic error was involved in the ultimate formation of the extra isochromosome.
Asunto(s)
Anomalías Múltiples/genética , Aneuploidia , Cromosomas Humanos Par 12 , Anomalías Múltiples/diagnóstico por imagen , Adulto , Alelos , Amniocentesis , Centrómero/ultraestructura , ADN Satélite , Femenino , Feto/anomalías , Feto/fisiología , Marcadores Genéticos , Homocigoto , Humanos , Hibridación in Situ , Cariotipificación , Masculino , Meiosis , Mitosis , Reacción en Cadena de la Polimerasa , Embarazo , Diagnóstico Prenatal , UltrasonografíaRESUMEN
The phenotypically normal sister of a patient affected by fragile X syndrome was referred for genetic counselling and was found to carry a mosaic karyotype 46,X,r(X)/45,X. Because the probability of the simultaneous chance occurrence of fragile X syndrome and a ring chromosome X in the same family is very low, we postulated that the breakpoint of the ring chromosome X originated in the cytogenetic break in Xq27.3 responsible for fragile X syndrome. In order to determine the relative positions of the breakpoint on the ring chromosome X and the (CGG)n unstable sequence responsible for the fragile X mutation, we used molecular markers to analyse the telomeric regions of chromosome X in this family. The results showed that the ring chromosome X was the maternal fragile X chromosome and that the telomeric deletion on the long arm encompassed the (CGG)n sequence. This suggests that the cytogenetic break in Xq27.3 is distinct from the unstable (CGG)n sequence, or that the break followed by the end-to-end fusion creating the ring chromosome was not completely conservative. Analysis of DNA markers on the short arm of chromosome X evidenced a deletion of a large part of the pseudoautosomal region, allowing us to position the genes involved in stature and in some syndromes associated with telomeric deletions of Xp on the proximal side of the pseudoautosomal region.
Asunto(s)
Síndrome del Cromosoma X Frágil/genética , Cromosomas en Anillo , Cromosoma X , Adulto , Southern Blotting , Deleción Cromosómica , ADN/análisis , Femenino , Marcadores Genéticos , Humanos , Cariotipificación , Masculino , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
In order to better characterize the chromosomic rearrangement of an unbalanced 45XX t(X;22) (q28;q11) DiGeorge patient, a somatic hybrid clone segregating the translocated chromosome was constructed and investigated using X and 22 linked markers. Our study demonstrated that this de novo translocation was from paternal origin. The breakpoint was assigned between DXS296 and IDS loci at Xq28 and between D22S9 and BCRL2 at 22q11. This observation and published data allow to locate a "critical region" for DiGeorge syndrome between these two last loci on 22q11. Our hybrid clone may be a useful tool for mapping new probes arising in this region.
Asunto(s)
Cromosomas Humanos Par 22 , Síndrome de DiGeorge/genética , Translocación Genética/genética , Cromosoma X , Southern Blotting , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Hibridación GenéticaRESUMEN
Interferon gamma (IFN-gamma) induces expression of class II major histocompatibility complex (MHC)-encoded antigens in immunocompetent cells. To gain further insight into the mechanism of this induction, we prepared somatic cell hybrids between different human cell lines and a murine cell line, RAG, that does not express murine class II MHC antigens before or after treatment with murine IFN-gamma. Some of the resulting cell hybrids express murine class II MHC antigens when treated with murine IFN-gamma. This inducible phenotype is correlated with the presence of human chromosome 16. It has been shown previously that the induction of class I MHC antigens by human IFN-gamma in human-rodent hybrids requires the presence of species-specific factors encoded by chromosome 6, which bears the gene for the human IFN-gamma receptor, and chromosome 21, whose product(s) is necessary for the transduction of human IFN-gamma signals. In this report, we show that the induction of murine class II MHC antigens by human IFN-gamma in the human-RAG cell hybrids requires, likewise, the presence of human chromosomes 6 and 21, in addition to chromosome 16. In some of these hybrids, when all three of these human chromosomes were present, induction of cell-surface HLA-DR antigens was also observed. Our results demonstrate that human chromosome 16 encodes a non-species-specific factor involved in the induction of class II MHC antigens by IFN-gamma.
Asunto(s)
Cromosomas Humanos Par 16 , Genes MHC Clase II/efectos de los fármacos , Antígenos HLA-D/genética , Interferón gamma/farmacología , Animales , Anticuerpos Monoclonales , Northern Blotting , Línea Celular , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Antígenos HLA-D/análisis , Antígenos de Histocompatibilidad Clase I , Humanos , Células Híbridas/citología , Células Híbridas/inmunología , Ratones , Proteínas Recombinantes , TransfecciónRESUMEN
Seventy-one human x mouse hybrid cell lines were used to map the locus of a human alpha-3-fucosyltransferase to 11q. The enzyme transfers fucose onto H type 2 more efficiently than onto sialyl-N-acetyllactosamine, suggesting that it is the myeloid type of alpha-3-fucosyltransferase (Mollicone et al., 1990), which makes the 3-fucosyllactosamine epitope on polymorphonuclear cells and monocytes. This epitope is also known as CD15 (Tetteroo et al., 1987).
Asunto(s)
Cromosomas Humanos Par 11 , Fucosiltransferasas/genética , Animales , Antígenos de Diferenciación/biosíntesis , Southern Blotting , Secuencia de Carbohidratos , Mapeo Cromosómico , Humanos , Células Híbridas , Antígeno Lewis X , Ratones , Datos de Secuencia Molecular , Hibridación de Ácido NucleicoRESUMEN
X; autosomal translocations are excellent tools for genetic analysis because of the easy selection of clones isolating the derivative bearing the HPRT gene in somatic cell hybrids. We have developed a strategy to select clones isolating the other derivative avoiding fastidious and time consuming technics, mainly based on immunofluorescent screening using MIC 2 and MIC 5 antigenic markers and we have succeeded in isolating in a rodent context the two X;5 translocated derivative chromosomes of a female patient with Hunter syndrome. The location of MIC 5 gene was specified between the IDS and G6PD DXS369 (RN1), DXS296 (VK21c), and DXS304 (U62), DXS52 and F8c (F814) are proximal and distal from the breakpoint disrupting the IDS gene respectively.
Asunto(s)
Células Híbridas/ultraestructura , Mucopolisacaridosis II/genética , Translocación Genética/genética , Cromosoma X , Anticuerpos Monoclonales , Southern Blotting , Fusión Celular , Línea Celular , Células Clonales , Femenino , Técnica del Anticuerpo Fluorescente , HumanosRESUMEN
A panel of 27 rodent-human somatic cell hybrids composed of cells of hematopoietic (nonadherent cells) and nonhematopoietic origin (adherent cells) was used to identify the chromosomes involved in the biological response to human IFN-gamma (Hu-IFN-gamma). We found that the stimulation of class-I histocompatibility antigen expression correlates with the presence of human chromosomes 6 and 21 in adherent cell hybrids, while human chromosome 6 alone is sufficient in nonadherent hybrids. Scatchard analysis of the binding of radiolabeled Hu-IFN-gamma to nonadherent cell hybrids gave a Kd value similar to that found on human cell lines. Induction of a reporter gene placed under the transcriptional control of the interferon responsive sequence (IRS) in adherent cell hybrids requires both chromosomes 6 and 21. The antiviral protection by Hu-IFN-gamma in adherent cell hybrids was reached at physiological doses (2 units/ml) when human chromosomes 6 and 21 were present, while higher doses of Hu-IFN-gamma (5000 units/ml) were required for hybrids lacking chromosome 21. Thus, we demonstrate that differences exit in the response to Hu-IFN-gamma depending on the origin of the cell type.
Asunto(s)
Cromosomas Humanos Par 21 , Cromosomas Humanos Par 6 , Células Madre Hematopoyéticas/metabolismo , Interferón gamma/farmacología , Animales , Anticuerpos Monoclonales/inmunología , Línea Celular , Resistencia a Medicamentos/genética , Técnica del Anticuerpo Fluorescente , Células Madre Hematopoyéticas/citología , Herpesvirus Humano 4 , Antígenos de Histocompatibilidad Clase I/biosíntesis , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Células Híbridas , Transfección , Virus de la Estomatitis Vesicular IndianaRESUMEN
The short arm of chromosome 11 carries genes involved in malformation syndromes, including the aniridia/genitourinary abnormalities/mental retardation (WAGR) syndrome and the Beckwith-Wiedemann syndrome, both of which are associated with an increased risk of childhood malignancy. Evidence comes from constitutional chromosomal aberrations and from losses of heterozygosity, limited to tumor cells, involving regions 11p13 and 11p15. In order to map the genes involved more precisely, we have fused a mouse cell line with cell lines from patients with constitutional deletions or translocations. Characterization of somatic cell hybrids with 11p-specific DNA markers has allowed us to subdivide the short arm into 11 subregions, 7 of which belong to band 11p13. We have thus defined the smallest region of overlap for the Wilms' tumor locus bracketed by the closest proximal and distal breakpoints in two of these hybrids. The region associated with the Beckwith-Wiedemann syndrome spans the region flanked by two 11p15.5 markers, HRAS1 and HBB. These hybrids also represent useful tools for mapping new markers to this region of the human genome.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 11/ultraestructura , Anticuerpos Monoclonales , Southern Blotting , Deleción Cromosómica , Sondas de ADN , Femenino , Marcadores Genéticos , Humanos , Células Híbridas , Masculino , SíndromeRESUMEN
Genetic analysis of the cells of a WAGR patient (W, predisposition to Wilms tumor; A, aniridia; G, genitourinary abnormalities; R, mental retardation), bearing a partial deletion of band 11p13, was performed with biochemical and antigenic 11p markers by using gene dosage, somatic hybridization, molecular hybridization, and indirect immunofluorescence techniques. These studies allowed the regional assignment of the gene for catalase, which is linked to the Wilms tumor locus, between MIC4 and MIC11, two loci encoding for membrane antigens previously mapped to band 11p13.
Asunto(s)
Antígenos/genética , Catalasa/genética , Cromosomas Humanos Par 11 , Niño , Deleción Cromosómica , Mapeo Cromosómico , Femenino , Marcadores Genéticos , Humanos , Discapacidad Intelectual/genética , Iris/anomalías , Neoplasias Renales/genética , Polimorfismo Genético , Síndrome , Anomalías Urogenitales , Tumor de Wilms/genéticaAsunto(s)
Hipertensión Portal/etiología , Vena Porta , Trombosis/complicaciones , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Hipertensión Portal/cirugía , Masculino , Venas Mesentéricas/cirugía , Persona de Mediana Edad , Derivación Esplenorrenal Quirúrgica , Venas Cavas/cirugíaRESUMEN
271 patients have been submitted to prostatic needle biopsy between january 1973 and september 1984. Sensitivity and specificity of transperineal prostatic biopsy for prostatic carcinoma are respectively 89% and 98%. Complications are met in 10% of these cases. Rectal examination has been compared to these results. Sensitivity is 75% and specificity 70%. Prostatic biopsy appears to be a good method for diagnosis of prostatic carcinoma but less effective than fine needle aspiration for cytologic examination.
Asunto(s)
Próstata/patología , Neoplasias de la Próstata/patología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja/efectos adversos , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/patología , Estudios RetrospectivosRESUMEN
Calcified intraluminal meconium is rarely observed in newborn. Only 27 cases are related in litterature; the authors report 4 new cases and point out the role of intestinal obstruction (principaly anorectal malformations, but also atresia, meconium ileus or Hirschsprung disease). Pathogenesis is unknown, while intestinal urinary fistula is frequently described.
Asunto(s)
Anomalías Múltiples/complicaciones , Calcinosis/congénito , Anomalías del Sistema Digestivo , Obstrucción Intestinal/congénito , Meconio , Calcinosis/complicaciones , Humanos , Recién Nacido , Fístula Intestinal/complicaciones , Obstrucción Intestinal/complicaciones , Masculino , Fístula Urinaria/complicaciones , Sistema Urinario/anomalíasAsunto(s)
Glándulas Suprarrenales/patología , Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/inmunología , Antígenos HLA/genética , Esteroide Hidroxilasas/deficiencia , Hiperplasia Suprarrenal Congénita/enzimología , Hiperplasia Suprarrenal Congénita/genética , Femenino , Francia , Ligamiento Genético , Antígenos HLA-B , Humanos , Hiperplasia , MasculinoRESUMEN
Determination of HLA antigens can be used for prenatal diagnosis of some congenital anomalies such as adrenal hyperplasia (21-hydroxylase deficiency). This necessitates rigourous HLA typing of fetal cells cultivated in vitro. The method we have developed utilizes microcytotoxicity and quantitative microabsorption tests which have been adapted to the types of cells found in these cultures.
Asunto(s)
Líquido Amniótico/citología , Antígenos HLA/análisis , Diagnóstico Prenatal/métodos , Absorción , Recuento de Células , Pruebas Inmunológicas de Citotoxicidad , Femenino , Humanos , EmbarazoRESUMEN
HLA markers (A, B, C, DR loci) were determined for the members of 52 unrelated families with at least one child suffering from congenital adrenal hyperplasia due to 21 hydroxylase deficiency, permitting genotyping. The gene frequencies of the 52 index cases were compared with those obtained from the patients' normal haplotypes and with those of a control reference panel. No significant differences were observed, except a clear decrease in the frequency of HLA-B8 among the haplotypes that carry the gene for congenital adrenal hyperplasia.