RESUMEN
In this case report we describe a 67-year-old male, admitted to the ICU with pneumonia who unexpectedly developed a fatal coma due to hyperammonaemia. At postmortem the diagnosis late-onset ornithine transcarbamylase deficiency was made. The non-specific clinical presentation, the rapid deterioration and incidentally the fatal outcome all underline the importance of recognition and knowledge of this genetic disorder. Several measures to treat and prevent potentially fatal episodes of hyperammonaemia are available, if only the disorder is recognised in time. In retrospect, several clues to the diagnosis were available in this fatal case, such as voluntary protein avoidance, as well as several male family members who died at a young age of an unknown cause. After his death, two daughters were discovered to be carriers of an OTC gene mutation, as well as his infant grandson. We emphasise the importance of obtaining ammonia levels in all patients with unexplained coma, seizures or cerebral oedema, irrespective of their age, especially in patients in the ICU or in an otherwise catabolic state.
Asunto(s)
Diagnóstico Tardío , Hiperamonemia/genética , Enfermedades de Inicio Tardío/genética , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/complicaciones , Anciano , Coma/genética , Resultado Fatal , Humanos , Masculino , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/diagnósticoRESUMEN
The Aspergillus niger trpC gene was isolated by complementation experiments with an Escherichia coli trpC mutant. Plasmid DNA containing the A. niger trpC gene transforms an Aspergillus nidulans mutant strain, defective in all three enzymatic activities of the trpC gene, to Trp+, indicating the presence of a complete and functional trpC gene. Southern blot analysis of DNA from these Trp+ transformants showed that plasmid DNA was present but that this DNA was not integrated at the site of the chromosomal trpC locus. The A. niger trpC gene was localized on the cloned fragment by heterologous hybridization experiments and sequence analysis. These experiments suggest that the organization of the A. niger trpC gene is identical to that of the analogous A. nidulans trpC and the Neurospora crassa trp-1 genes.
Asunto(s)
Isomerasas Aldosa-Cetosa , Antranilato Sintasa , Aspergillus niger/genética , Genes Fúngicos , Transferasas de Grupos Nitrogenados , Triptófano/genética , Secuencia de Bases , Carbohidrato Epimerasas/genética , Mapeo Cromosómico , Indol-3-Glicerolfosfato Sintasa/genética , Neurospora crassa/genética , Hibridación de Ácido Nucleico , Selección Genética , Homología de Secuencia de Ácido Nucleico , Transferasas/genéticaRESUMEN
A genetic transformation system for the aflatoxin-producing fungus Aspergillus parasiticus using two autonomously replicating plasmids from A. nidulans (ARp1 and pDHG25) is reported. Transformation frequencies using the plasmid pDHG25 were from 5 x 10(2) to 2.5 x 10(4) transformants per 10(6) viable protoplasts and microgram DNA. The stability of the plasmids in the transformants was also studied. This transformation system offers a new opportunity to clone genes related to aflatoxin production using appropriate aflatoxin-defective mutants.
Asunto(s)
Aspergillus nidulans/genética , Aspergillus/genética , Replicación del ADN , Plásmidos , Transformación Genética , ADN de Hongos/análisis , Mitosis , Plásmidos/genética , ProtoplastosRESUMEN
Semi-logarithmic dose-response curves for survival of UV-irradiated conidiospores of A. nidulans have an initial shoulder (at low doses) followed by a decline which becomes linear. To explain the initial shoulder and the resulting extrapolation number (log S intercept of the linear extrapolation line) a general model is presented, which includes multi-target (n) and multi-hit (h) effects and allows for the effect of initial repair and of a compound parameter k, which stands for inherent sensitivity of the spores and for dose received inside the spores. From experiments on (a) the modification of k (spore wall colour and shelter effects), (b) a repair-deficient strain (shoulderless) and (c) preincubation during which DNA-replication takes place, it is concluded that the shoulder is generated by initial repair rather than by a multi-hit nature of the cell-killing process. In experiments where k takes different values (sub a and c), notably the position of the point of intersection of the linear lines gives conclusive information. In general, the log S intercept of the linear extrapolation line cannot be used to estimate the target number.
Asunto(s)
Aspergillus nidulans/efectos de la radiación , Rayos Ultravioleta , Aspergillus nidulans/genética , Aspergillus nidulans/crecimiento & desarrollo , Reparación del ADN , Relación Dosis-Respuesta en la Radiación , Mutación , Especificidad de la EspecieRESUMEN
We report on a patient with sensorineural deafness, onycho- and osteodystrophy and mental retardation (DOOR syndrome) and review the literature. It appears that abnormal dermatoglyphics are a frequent feature of the DOOR syndrome, as all patients with DOOR syndrome in whom dermatoglyphic investigations were done, had multiple arches on their fingertips.
Asunto(s)
Enfermedades Óseas/diagnóstico por imagen , Sordera , Discapacidad Intelectual/diagnóstico , Enfermedades de la Uña/diagnóstico , Preescolar , Dermatoglifia , Dedos/anomalías , Humanos , Masculino , Radiografía , SíndromeRESUMEN
Somatic cells of males with azoospermia or oligozoospermia (sperm density < 20 million sperm cells/ml) were found to contain increased percentages of chromosomal abnormalities. Subfertile males with a normal somatic karyogram were found to have increased rates of aneuploidy in sperm. This creates risks for the offspring after fertilization with intracytoplasmatic sperm injection (ICSI). Certain gene mutations on the Y chromosome cause severe oligo- or azoospermia and will, in case of successful reproduction with ICSI, be transmitted to male offspring in 100% of the cases. The same holds true, irrespective of sex, of mutations responsible for cystic fibrosis. In non-random groups of ICSI pregnancies, higher proportions of de novo sex-chromosomal abnormalities have been found than expected. In addition, there are increased proportions of paternally inherited structural autosomal anomalies. Extrapolation of the findings is not yet possible, however.
Asunto(s)
Aberraciones Cromosómicas , Trastornos de los Cromosomas , Fertilización In Vitro/métodos , Oligospermia/etiología , Humanos , Masculino , MicroinyeccionesRESUMEN
The genetics of A. niger has been developed since 1980. An overview is presented of the advances in developing methods and collecting data. Important tools have been a) the application of essentially different methods to isolate mutants, b) the adaptation to A. niger ofA. nidulans methodology for analysis of the parasexual cycle, c) the choice of marker genes, and in some cases the artificial introduction of such genes, to select homozygous segregants arising from mitotic recombination. With the use of parasexual recombination, a genetic linkage map of A. niger has been established. In total, 110 nuclear and 1 cytoplasmic (mitochondrial) markers are available. The application of A. niger genetics in applied research is illustrated by examples.
Asunto(s)
Aspergillus niger/genética , Mapeo Cromosómico , Ligamiento Genético , Marcadores Genéticos , Cariotipificación , Mutación , Selección GenéticaAsunto(s)
Adenosina Trifosfatasas , Lípidos , Hígado/enzimología , Membranas/enzimología , Nucleotidasas , Fosfolipasas , Monoéster Fosfórico Hidrolasas , Adenosina Trifosfatasas/antagonistas & inhibidores , Animales , Magnesio , Ácidos Neuramínicos , Neuraminidasa , Nucleotidasas/antagonistas & inhibidores , Fosfatidilcolinas , Fosfolipasas/antagonistas & inhibidores , Monoéster Fosfórico Hidrolasas/antagonistas & inhibidores , Ratas , Albúmina SéricaAsunto(s)
Adenosina Trifosfatasas/metabolismo , Membrana Celular/enzimología , Hígado/citología , Hígado/enzimología , Magnesio , Nucleotidasas/metabolismo , Potasio , Sodio , Animales , Busulfano/farmacología , Cloromercuribenzoatos/farmacología , Cisteína/farmacología , Enzimas/farmacología , Técnicas In Vitro , Ácidos Oléicos/farmacología , Oligomicinas/farmacología , Ouabaína/farmacología , Ratas , Tensoactivos/farmacología , UltrasonidoAsunto(s)
Membrana Celular/enzimología , Gangliósidos/farmacología , Hígado/citología , Magnesio/metabolismo , Ácidos Neuramínicos/metabolismo , Neuraminidasa/farmacología , Monoéster Fosfórico Hidrolasas/metabolismo , Potasio/metabolismo , Animales , Transporte Biológico Activo , Técnicas In Vitro , RatasAsunto(s)
Calcio/farmacología , Membrana Celular/enzimología , Cloromercuribenzoatos/farmacología , Hígado/citología , Hígado/enzimología , Neuraminidasa/farmacología , Monoéster Fosfórico Hidrolasas/metabolismo , Potasio/farmacología , Sodio/farmacología , Animales , Técnicas In Vitro , Ouabaína/farmacología , Péptidos/farmacología , RatasAsunto(s)
Adenilil Ciclasas , Carcinoma Hepatocelular/enzimología , Membrana Celular/enzimología , Epinefrina/farmacología , Glucagón/farmacología , Hormona del Crecimiento/farmacología , Insulina/farmacología , Hígado/enzimología , Adenosina Trifosfato , Animales , Isótopos de Carbono , AMP Cíclico , Ácido Edético/farmacología , Activación Enzimática , Femenino , Fluoruros/farmacología , Técnicas In Vitro , Hígado/citología , Neoplasias Hepáticas , Masculino , Métodos , Ratones , Neoplasias Experimentales/enzimología , Ratas , Sodio/farmacología , TritioAsunto(s)
Fosfatasa Alcalina/metabolismo , Carcinoma Hepatocelular/enzimología , Membrana Celular/enzimología , Hígado/enzimología , Fosfatasa Ácida/metabolismo , Animales , Calcio/farmacología , Carcinógenos/farmacología , Castración , Colesterol/farmacología , Ácido Edético/farmacología , Estrona/farmacología , Femenino , Glicerofosfatos , Hígado/citología , Neoplasias Hepáticas , Magnesio/farmacología , Masculino , Neoplasias Experimentales/enzimología , Nitrofenoles , Fenobarbital/farmacología , Potasio/farmacología , Ratas , Factores Sexuales , Testosterona/farmacología , Zinc/farmacologíaAsunto(s)
Carcinoma Hepatocelular/patología , Membrana Celular , Hígado/citología , Animales , Calcio , Carcinoma Hepatocelular/análisis , Fraccionamiento Celular/métodos , Membrana Celular/análisis , Membrana Celular/enzimología , Membrana Celular/ultraestructura , Centrifugación por Gradiente de Densidad , ADN/análisis , Enzimas/análisis , Femenino , Lípidos/análisis , Hígado/análisis , Hígado/enzimología , Hígado/patología , Neoplasias Hepáticas , Ratones , Ratones Endogámicos CBA , Microscopía Electrónica , Mitocondrias Hepáticas , Proteínas de Neoplasias/análisis , Neoplasias Experimentales/patología , Proteínas/análisis , ARN/análisis , Ratas , Especificidad de la Especie , Fracciones SubcelularesAsunto(s)
Carcinógenos/farmacología , Colchicina/farmacología , Citocalasina B/farmacología , Diterpenos/farmacología , Glucagón/farmacología , Hígado/enzimología , Mitosis/efectos de los fármacos , Vinblastina/farmacología , Adenosina Trifosfatasas/metabolismo , Adenilil Ciclasas/metabolismo , Alcoholes/farmacología , Animales , Membrana Celular/efectos de los fármacos , Membrana Celular/enzimología , Dimetilsulfóxido/farmacología , Femenino , Fluoruros/farmacología , Hígado/citología , Hígado/efectos de los fármacos , Masculino , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/enzimología , Ratones , Hidrolasas Diéster Fosfóricas/metabolismo , Ratas , Factores de TiempoAsunto(s)
Ergotamina/análisis , Cromatografía en Capa Delgada , Fluorescencia , Métodos , Soluciones , ComprimidosRESUMEN
We report on a child who presented clinical manifestations of both neurofibromatosis type 1 (NF1) and cherubism. With genetic testing, we found a mutation in the NF-1 gene, confirming the neurocutaneous disorder. Histology when correlated with radiological evaluation of a mandibular biopsy was consistent with cherubism. This is the first report in the literature of a child with proven neurofibromatosis type 1 and cherubism without extragnathic lesions. This emphasises that cherubism is a clinical phenotype that can be associated with a number of germline mutations involving SH3BP2, PTPN11 and NF1.