RESUMEN
Chromosome microarrays are an essential tool for investigation of copy number changes in children with congenital anomalies and intellectual deficit. Attempts to standardise microarray testing have focused on establishing technical and clinical quality criteria, however external quality assessment programs are still needed. We report on a microarray proficiency testing program for Australasian laboratories. Quality metrics evaluated included analytical accuracy, result interpretation, report completeness, and laboratory performance data: sample numbers, success and abnormality rate and reporting times. Between 2009 and 2014 nine samples were dispatched with variable results for analytical accuracy (30-100%), correct interpretation (32-96%), and report completeness (30-92%). Laboratory performance data (2007-2014) showed an overall mean success rate of 99.2% and abnormality rate of 23.6%. Reporting times decreased from >90 days to <30 days for normal results and from >102 days to <35 days for abnormal results. Data trends showed a positive correlation with improvement for all these quality metrics, however only 'report completeness' and reporting times reached statistical significance. Whether the overall improvement in laboratory performance was due to participation in this program, or from accumulated laboratory experience over time, is not clear. Either way, the outcome is likely to assist referring clinicians and improve patient care.
Asunto(s)
Ensayos de Aptitud de Laboratorios/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/normas , Australasia , Dosificación de Gen , Humanos , Laboratorios/normasRESUMEN
We report on a 4-year-old male with an interstitial tandem duplication of Xq21.1-q21.31 who presented with clinical features of Prader-Willi syndrome (PWS). The duplication was maternally inherited. Abnormalities of the X chromosome have previously been reported in association with a PWS phenotype, but to date, specific duplications of Xq21.1-q21.31 have not. We refined the chromosomal breakpoints seen on initial G-banded karyotyping in our case with comparative genomic hybridization by microarray (array CGH). The duplication was between 11.1 and 14.4 Mb in length and overlaps with three loci to which mental retardation with PWS-like features have been previously mapped, showing the utility of array CGH in helping to identify candidate genes. We conclude that duplication of chromosomal region Xq21.1-q21.31 potentially results in a PWS-like phenotype. Reviewing the literature on similar duplications, we further conclude that distal Xq duplications can result in features typically seen in infants with PWS, while proximal duplications can result in features typically seen in older children and adults with PWS. Duplications of chromosome Xq should be considered in the differential diagnosis of PWS, especially in males.
Asunto(s)
Cromosomas Humanos X/genética , Duplicación de Gen , Síndrome de Prader-Willi/genética , Preescolar , Bandeo Cromosómico , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Hibridación de Ácido NucleicoRESUMEN
A small, mosaic, C-band negative marker chromosome was detected in amniocyte cultures during prenatal diagnosis due to advanced maternal age. Following spontaneous premature labor at 29 weeks gestation, a dysmorphic infant was delivered, with flat nasal bridge, short palpebral fissures, micrognathia, high forehead, low-set ears, telecanthus and corneal dystrophy. Additional folds of skin were present behind the neck, and feet, fingers and toes were abnormally long. The child died at age five days, after two days of renal failure. The origin of the marker chromosome was subsequently identified from a cord blood sample, via chromosome microdissection. Through reverse FISH, we found the marker to be an inverted duplication of the region 15q26.1-->qter. FISH with alphoid satellite probe was negative, while whole chromosome 15 paint was positive. Both ends of the marker chromosome were positive for the telomeric TTAGGG probe. These data, plus the G-banding pattern, identified the marker as an analphoid, inverted duplicated chromosome, lacking any conventional centromere. We discuss the etiology and clinical effects of this marker chromosome, comparing it to the few reported cases of "tetrasomy 15q" syndrome. We also discuss the possible mechanisms that are likely responsible for this neocentromere formation.
Asunto(s)
Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 15/genética , Diagnóstico Prenatal/métodos , Resultado Fatal , Humanos , Recién Nacido , Masculino , Microdisección/métodosAsunto(s)
Infecciones Bacterianas del Ojo/diagnóstico , Enfermedades de la Retina/diagnóstico , Sífilis/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/microbiología , Humanos , Penicilinas/uso terapéutico , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/microbiología , Sífilis/tratamiento farmacológico , Sífilis/microbiología , Serodiagnóstico de la SífilisRESUMEN
OBJECTIVE: To evaluate the clinical presentation, treatment, and long-term follow-up of eyelid Merkel cell carcinoma. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Fourteen patients with primary eyelid Merkel cell carcinoma. METHODS: Cases of Merkel cell carcinoma for which long-term follow-up was available were solicited from members of the American Society of Ophthalmic Plastic and Reconstructive Surgery through an on-line e-mail/news group. MAIN OUTCOME MEASURES: Follow-up period, treatment history, presence and type of recurrence, and mortality. RESULTS: Average follow-up was 33.4 months. Of the 14 cases identified, only 2 patients (14%) received prophylactic therapy beyond wide surgical excision. Three patients (21%) had recurrences, none of whom initially received prophylactic therapy (i.e., radiation therapy, lymph node dissection, and/or chemotherapy) beyond wide surgical excision. One patient (7%) died of metastatic Merkel cell carcinoma. CONCLUSIONS: Merkel cell carcinoma is a rare skin malignancy that occasionally affects the eyelid, with the potential for regional and distant metastasis. Consideration should be given to the use of prophylactic adjunctive therapies beyond wide surgical excision while simultaneously considering the morbidity of these therapies.
Asunto(s)
Carcinoma de Células de Merkel/diagnóstico , Neoplasias de los Párpados/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/cirugía , Neoplasias de los Párpados/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Neoplasias Cutáneas/cirugíaRESUMEN
BACKGROUND: Strabismus and poverty are more common among developmentally delayed children. Poverty is difficult to define, but qualification for Medicaid benefits has been used as an indicator in the past. METHODS: There was a retrospective review of 95 patients with strabismus younger than 7 years who were seen in the Department of Pediatric Ophthalmology at the Albany Medical Center for a 12-month period and were reviewed for the presence or absence of developmental delay. These patients were selected from 2 groups: one with Medicaid coverage and one without. RESULTS: Developmental delays were noted in 13 patients without Medicaid (27.0%) and in 26 patients with Medicaid (55.3%) (P = .0096). Patients with Medicaid were less likely to name Allen pictures by age 3 years (P = .0003). CONCLUSIONS: Poverty is more commonly associated with delays in patients with strabismus, and this should alert ophthalmologists who work with Medicaid patients to seek to identify the presence of developmental delay in managing the care of these patients.
Asunto(s)
Discapacidades del Desarrollo/etiología , Pobreza , Estrabismo/etiología , Niño , Preescolar , Discapacidades del Desarrollo/economía , Discapacidades del Desarrollo/epidemiología , Humanos , Lactante , Medicaid/economía , Medicaid/legislación & jurisprudencia , New York/epidemiología , Pobreza/economía , Pobreza/legislación & jurisprudencia , Prevalencia , Estudios Retrospectivos , Estrabismo/economía , Estrabismo/epidemiología , Estados UnidosRESUMEN
We determined the breakpoint genes of the translocation t(4;11)(q21;p15) that occurred in a case of adult T-cell acute lymphocytic leukemia (T-ALL). The chromosome 11 breakpoint was mapped to the region between D11S470 and D11S860. The nucleoporin 98 gene (NUP98), which is rearranged in several acute myeloid leukemia translocations, is located within this region. Analysis of somatic cell hybrids segregating the translocation chromosomes showed that the chromosome 11 breakpoint occurs within NUP98. The fusion partner of NUP98 was identified as the RAP1GDS1 gene using 3' RACE. RAP1GDS1 codes for smgGDS, a ubiquitously expressed guanine nucleotide exchange factor that stimulates the conversion of the inactive GDP-bound form of several ras family small GTPases to the active GTP-bound form. In the NUP98-RAP1GDS1 fusion transcript (abbreviated as NRG), the 5' end of the NUP98 gene is joined in frame to the coding region of the RAP1GDS1 gene. This joins the FG repeat-rich region of NUP98 to RAP1GDS1, which largely consists of tandem armadillo repeats. NRG fusion transcripts were detected in the leukemic cells of 2 other adult T-ALL patients. One of these patients had a variant translocation with a more 5' breakpoint in NUP98. This is the first report of an NUP98 translocation in lymphocytic leukemia and the first time that RAP1GDS1 has been implicated in any human malignancy.
Asunto(s)
Cromosomas Humanos Par 11 , Cromosomas Humanos Par 4 , Proteínas de Unión al GTP/genética , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas de la Membrana/genética , Proteínas de Complejo Poro Nuclear , Proteínas Nucleares/genética , Proteínas/genética , Translocación Genética , Adolescente , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Mapeo Cromosómico , Femenino , Marcadores Genéticos , Factores de Intercambio de Guanina Nucleótido , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia-Linfoma de Células T del Adulto/inmunología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Especificidad de Órganos , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas/genética , Transcripción Genética , Proteínas de Unión al GTP rap , Factores de Intercambio de Guanina Nucleótido rasRESUMEN
E1000, the most drug-resistant subline from the E-series (CCRF-CEM/E16 to E1000), has been previously shown to express high mRNA levels from two ABC transporter genes associated with multidrug resistance, ARA and MRP. The expression and amplification of both genes has now been characterized for each member of the E-series of drug-resistant sublines and is reported here. Both ARA [detected by reverse transcriptase polymerase chain reaction (RT-PCR)] and MRP (detected by Northern blot analysis) were expressed at low levels in the sensitive parental CEM cell line. An equivalent level of MRP mRNA expression was detected throughout the CEM, E16, E25 and E50 sublines, and there was increasing expression in the E100, E200 and E1000 sublines. ARA expression was not detected in the E16, E25, E50 and E100 sublines but was detected by both RT-PCR and Northern blot analysis in the E200 and E1000 sublines. Southern blot analysis indicated the increased levels of MRP and ARA expression resulted from gene amplification and that MRP was first amplified in the E100 subline and ARA in the E200 subline, suggesting that the two genes were not initially co-amplified. Cytogenetic analysis of E1000 cells demonstrated a large addition to chromosome 16p, around the region where the ARA and MRP genes are located. Increased expression of ARA is associated with increased colchicine resistance in the E-series of sublines and combined with MRP may account for their resistance phenotype.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/biosíntesis , Resistencia a Múltiples Medicamentos/genética , Leucemia de Células T/genética , Leucemia de Células T/metabolismo , Proteínas de Neoplasias/biosíntesis , Transportadoras de Casetes de Unión a ATP/genética , Antibióticos Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Amplificación de Genes , Expresión Génica , Humanos , Leucemia de Células T/tratamiento farmacológico , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Proteínas de Neoplasias/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Transcripción Genética , Células Tumorales CultivadasRESUMEN
cDNA clones corresponding to the sequence for human early pregnancy factor were isolated from a human melanoma library and hybridized to DNA digested with four restriction enzymes obtained from twelve different subjects. Up to 20 cross hybridizing bands were observed. When hybridized to metaphase spreads from four different humans, significant signals were present in nine locations, on eight different chromosome arms. These results suggest that the early pregnancy factor gene is a member of a large gene family. The coding sequence for early pregnancy factor has a high degree of homology with the sequence for human chaperonin 10, and the gene family described here should contain the genes for both of these proteins.
Asunto(s)
Chaperonina 10/genética , Tolerancia Inmunológica/genética , Péptidos/genética , Proteínas Gestacionales , Factores Supresores Inmunológicos , Southern Blotting , Mapeo Cromosómico , ADN Complementario/química , Femenino , Humanos , Sistemas de Lectura Abierta , Reacción en Cadena de la Polimerasa , Embarazo , Mapeo Restrictivo , Células Tumorales CultivadasAsunto(s)
Aberraciones Cromosómicas , Fertilización In Vitro/efectos adversos , Fertilización In Vitro/métodos , Microinyecciones , Aberraciones Cromosómicas Sexuales/etiología , Aneuploidia , Citoplasma , Femenino , Asesoramiento Genético , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/terapia , Masculino , Factores de RiesgoAsunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 9 , Leucemia Mieloide/genética , Células 3T3 , Animales , Secuencia de Bases , Bandeo Cromosómico , Femenino , Humanos , Células Híbridas , Masculino , Ratones , Regiones Promotoras Genéticas , Mapeo Restrictivo , Homología de Secuencia de Ácido NucleicoRESUMEN
We describe the localization of the chromosome 11 breakpoint of a T-ALL translocation, t(4;11)(q21;p14-15), to sub-band 11p15.5. The breakpoint is located between the genes for insulin-like growth factor II (IGFII) and the M1 subunit of ribonucleotide reductase (RRM1). This region does not include any previously cloned genes involved in cancer.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 4 , Leucemia-Linfoma de Células T del Adulto/genética , Translocación Genética , Animales , Secuencia de Bases , Cartilla de ADN , Humanos , Ratones , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
A 21-year-old male presented with a large mediastinal mass and a white cell count of 420 x 10(9)/L. A diagnosis of acute lymphoblastic leukemia (ALL) was made, with 90% of cells in the bone marrow (BM) and 99% in the peripheral blood (PB) being lymphoblasts (FAB L1). Cytogenetic analysis of these cells revealed a rare variant of the t(4;11) translocation involving chromosome arm 11p rather than 11q, namely t(4;11)(q21;p14-15). The standard form of the (4;11) translocation has been associated with leukemias with mixed-lineage phenotypes. Three cases of ALL with t(4q;11p) have previously been reported. One of these cases showed phenotypic heterogeneity involving myeloid and lymphoid lineages. The leukemia reported here also exhibits lymphoid/myeloid features. Immunophenotyping of the blasts showed that most of the cells were positive for CD2, CD5, CD7, CD10 (CALLA), CD34, and HLA-DR. A significant proportion of the cells expressed CD33. These results suggest a biphenotypic rather than a biclonal disease. Molecular analysis showed rearrangement of both immunoglobulin heavy-chain genes (JH) and of a single allele of the T-cell receptor (TCR) gamma 1 gene, while retaining germline TCR beta genes.
Asunto(s)
Cromosomas Humanos Par 11 , Cromosomas Humanos Par 4 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocación Genética , Adulto , Antígenos CD/análisis , Reordenamiento Génico/genética , Reordenamiento Génico de Linfocito T , Antígenos HLA-DR/análisis , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunofenotipificación , Cariotipificación , Masculino , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
We present two cases in which translocations involving 21q22 were found at presentation in acute nonlymphocytic leukemia (ANLL). The first of these translocations, t(3;21)(q26-q27;q22), is previously unknown in ANLL, but appears indistinguishable from that reportedly associated with Philadelphia-positive chronic myelogenous leukemia. The second case involves t(15;21)(q21-q22;q22), a translocation previously undescribed in ANLL. Both of these exchanges involve 21q22 plus another chromosome region associated with leukemogenesis. We attempted to interrelate these cytogenetic data with the oncogenic significance of 21q22.
Asunto(s)
Cromosomas Humanos Par 21 , Leucemia Mieloide Aguda/genética , Translocación Genética , Bandeo Cromosómico , Femenino , Humanos , Cariotipificación , Leucemia Mielomonocítica Aguda/genética , Masculino , Persona de Mediana EdadAsunto(s)
Síndrome de Down/genética , Edad Materna , Mosaicismo , Adolescente , Adulto , Femenino , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , ProbabilidadRESUMEN
A system is proposed whereby human karyotype data is expressed in quantitative terms rather than in the ISCN (1985) terminology used at present. This recoding facilitates application of multivariate analysis using standard statistical packages. As an example, karyotypes of 714 cases from 11 leukemias (Mitelman, 1983) are here recorded and subjected to discriminant analysis (SPSSx, 1983). Significant karyotypic specificity is apparent in six of the 11 FAB leukemia types. Four others show insignificant levels of specificity, while the last is equivocal. These results merely confirm present views. However, their generation by means of computerized multivariate analysis is novel, and confirms the feasibility of the approach. In this quantitative form, karyotypic data may be combined with any other data of diagnostic or prognostic value. Given such a consolidated data set, desired information concerning any aspect of neoplasia could be extracted via a single procedure.
Asunto(s)
Aberraciones Cromosómicas , Trastornos de los Cromosomas , Leucemia/genética , Enfermedad Aguda , Análisis de Varianza , Humanos , Cariotipificación , Leucemia Linfoide/genética , Leucemia Mieloide/genéticaRESUMEN
When univalent chromosomes are present at first meiotic division, their behaviour is highly variable. In some cases, both sister kinetochores orient towards the same pole (syntely) while in others, the two kinetochores orient to opposite poles (amphitely). The former may be accompanied by recurrent pole-to-pole oscillation, although, as the present report suggests, this is not the only variation which can be found in conjunction with syntelic orientation. This study attempts to explain this diversity of orientation phenomena. A computer model was constructed which can generate all of the common univalent behaviours. Simulation experiments suggest that chromosome length is critical in determining whether amphitelic or syntelic orientation will predominate. Syntely should be common among large univalents, but oscillations will be rare or absent if the chromosome has any capacity for microtubule attachment at its non-centromeric end. It appears that gross attributes of the chromosome may influence the orientation of univalents during the first meiotic division, with consequent effects on the probability of transmission to the next generation.