Ictiosis ligada al x tratada con tazarotene tópico / X-linked ichthyosis treated with tazarotene topic

La Ictiosis ligada al cromosoma X (ILX), es una genodermatosis poco frecuente que afecta a varones, se manifiesta a partir del período neonatal y se caracteriza por: xerodermia, hiperqueratosis, descamación y en algunos casos, manifestaciones extracutáneas. La delección total o parcial de la enzima sulfatasa esteroidea, es la causa de las manifestaciones clínicas. Presentamos el caso clínico, de un paciente con manifestaciones clínicas y hallazgos en la anatomía patológica, compatibles con esta entidad tratado con tazarotene (gel).

X-linked ichthyosis (XLI) is a rare genodermatosis that affects men and manifests from the neonatal period and is characterized by xeroderma, hyperkeratosis, desquamation and in some cases, extracutaneous manifestations. The disease is of chronic evolution and undergoes partial improvement in the summer season. The total or partial deletion of the steroid sulphatase enzyme is the cause of the clinical manifestations. We present the case of a patient with clinical manifestations and findings in the pathological anatomy compatible with this entity, as well as ITS treatment with topical tazarotene 0.1% (gel) Weekly controls were performed and clinical benefit of lesion-free skin was observed up to 6 weeks after treatment discontinuation, followed by the progressive appearance of brownish scales that became thick and adherent with the passage of time.

Role of bone marrow tyrosine kinase on chromosome X in the production of pro-inflammatory cytokines from mouse mononuclear-macrophages RAW264.7 induced by endotoxin/lipopolysaccharide and its mechanism / 中华烧伤杂志

Objective@#To investigate the role of bone marrow tyrosine kinase on chromosome X (BMX) in the production of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) from mouse mononuclear-macrophages induced by endotoxin/lipopolysaccharide (LPS) and its related mechanism.@*Methods@#Mouse mononuclear-macrophages RAW264.7 were inoculated in 6-well plates and routinely cultured for the following experiments. (1) Cells were collected and divided into blank control group, LPS control group, and 75, 750, 7 500, 75 000 nmol/L BMX-IN-1 pretreatment groups according to the random number table, with 8 wells in each group. Cells in blank control group were routinely cultured for 25 h. Cells in LPS control group were routinely cultured for 24 h and stimulated by LPS in the final mass concentration (the same below) of 0.1 μg/mL for 1 h. Cells in the latter 4 groups were pretreated with BMX-IN-1 in the final molarity (the same below) of 75, 750, 7 500, 75 000 nmol/L for 24 h and stimulated by 0.1 μg/mL LPS for 1 h. The mRNA expression of TNF-α of cells in each group was determined by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) to screen the optimum concentration of BMX-IN-1. (2) Cells were collected and divided into LPS control group and 2, 4, 8, 12, 18 h BMX-IN-1 pretreatment groups according to the random number table, with 8 wells in each group. Cells in LPS control group were stimulated by 0.1 μg/mL LPS for 1 h. Cells in the latter 5 groups were pretreated with optimum concentration of BMX-IN-1 for 2, 4, 8, 12, 18 h respectively and stimulated by 0.1 μg/mL LPS for 1 h. The mRNA expression of TNF-α of cells in each group was determined by real-time fluorescent quantitative RT-PCR to screen the optimum time for BMX-IN-1 pre-treatment. (3) Cells were collected and divided into blank control group, BMX-IN-1 control group, LPS control group, and BMX-IN-1+ LPS group according to the random number table, with 16 wells in each group. Cells in blank control group were routinely cultured for the optimum time plus 1 h. Cells in BMX-IN-1 control group were pretreated with BMX-IN-1 in the optimum concentration for the optimum time and then routinely cultured for 1 h. Cells in LPS control group were routinely cultured for the optimum time and then stimulated by 0.1 μg/mL LPS for 1 h. Cells in BMX-IN-1+ LPS group were pretreated with BMX-IN-1 in the optimum concentration for the optimum time and then stimulated by 0.1 μg/mL LPS for 1 h. The mRNA expressions of TNF-α and IL-1β were determined by real-time fluorescent quantitative RT-PCR, and the activity of BMX and p38 mitogen-activated protein kinase (MAPK) were determined by Western blotting, with 8 samples in each determination. Data were processed with one-way analysis of variance and LSD test.@*Results@#(1) Compared with that in blank control group, the mRNA expression of TNF-α of cells was significantly increased in the other 5 groups (with P values below 0.01). Compared with that in LPS control group, the mRNA expression of TNF-α of cells was decreased in each BMX-IN-1 pretreatment group, but only the mRNA expression of TNF-α of cells in 75 000 nmol/L BMX-IN-1 pretreatment group was significantly decreased (P<0.05). The optimum concentration of BMX-IN-1 was 75 000 nmol/L. (2) Compared with that in LPS control group, the mRNA expression of TNF-α of cells was not significantly changed in 2 and 4 h BMX-IN-1 pretreatment groups (with P values above 0.05) but significantly decreased in 8, 12, and 18 h BMX-IN-1 pretreatment groups (P<0.05 or P<0.01). The mRNA expression of TNF-α of cells in 12 h BMX-IN-1 pretreatment group was the lowest. The optimum time for BMX-IN-1 pre-treatment was 12 h. (3) The mRNA expressions of TNF-α and IL-1β of cells in BMX-IN-1 control group were 0.97±0.13 and 0.98±0.06, respectively, which were similar to 1.00 of blank control group (with P values above 0.05). The mRNA expressions of TNF-α and IL-1β of cells in LPS control group were 2.97±0.17 and 3.07±0.60, respectively, while those in BMX-IN-1+ LPS group were 2.31±0.94 and 2.55±0.73, respectively, with the 4 values significantly higher than those in blank control group (with P values below 0.01). The mRNA expressions of TNF-α and IL-1β of cells in BMX-IN-1+ LPS group were significantly lower than those in LPS control group (with P values below 0.05). The activity values of BMX and p38MAPK of cells in BMX-IN-1 control group were 0.95±0.19 and 0.98±0.18, respectively, which were close to 1.00±0.14 and 1.00±0.22 of blank control group (with P values above 0.05). The activity values of BMX and p38MAPK of cells in LPS control group were 1.98±0.33 and 2.05±0.34, respectively, which were significantly higher than those of blank control group (with P values below 0.01). The activity values of BMX and p38MAPK of cells in BMX-IN-1+ LPS group were 1.00±0.17 and 1.67±0.27, respectively, which were obviously lower than those of LPS control group (P<0.05 or P<0.01).@*Conclusions@#BMX can increase the production of pro-inflammatory cytokines TNF-α and IL-1β from mouse mononuclear-macrophages induced by LPS, which may be associated with the activation of the p38MAPK pathway by BMX.

Caracterización clínico-epidemiológica y genética de una familia con retinosis pigmentaria recesiva ligada al cromosoma X / Clinical-Epidemiological Characterization and Genetics of a Family with Chromosome X-linked Recessive Retinitis Pigmentosa

Introducción: la retinosis pigmentaria es una enfermedad hereditaria, que afecta a fotorreceptores y el epitelio pigmentario y provoca una atrofia retiniana. La forma recesiva ligada al cromosoma X es la más severa en su evolución clínica. Esta enfermedad constituye un problema de salud en la provincia de Holguín. Objetivo: caracterizar clínica epidemiológica y genéticamente a esta familia con retinosis pigmentaria recesiva ligada al cromosoma X. Métodos: se realizó un estudio descriptivo, retrospectivo, que incluye a un total de 15 individuos, de ellos, siete enfermos, seis portadoras y dos posibles afectados, pertenecientes a una familia afectada con retinosis pigmentaria recesiva ligada al cromosoma X del municipio de Urbano Noris de la provincia Holguín. Con su consentimiento informado se le realizó examen oftalmológico detallado (campo visual, función retinal) y estudio genético que incluyó confección de árbol genealógico hasta la cuarta generación y extracción de sangre periférica, para análisis de ADN por técnica de reacción en cadena de la polimerasa, en el exón 15, del gen RPGR, que busca la mutación más frecuente. Resultados: predominó el grupo de las edades comprendidas entre 10-19 y 20-29 años, con el 28,57 % en ambos casos. La edad de comienzo fue precoz en la totalidad de los enfermos, las alteraciones vítreas predominaron en el 71,43 %. El 42,85 % de los enfermos estaba en el estadio final de la enfermedad y presentaron electrorretinograma no registrable el 71,43 %. El 60 % de las portadoras presentaron en el fondo de ojo lesiones pre-pigmento, reflejo tapetal, coincidiendo algunas con electrorretinogramas subnormales. Conclusiones: el debut de la enfermedad se presentó de forma precoz. Entre las características clínicas prevalecieron las alteraciones vítreas y electrorretinograma no registrable. La mayoría de los pacientes se encontraban en el estadio IV de la enfermedad. Las lesiones en el fondo de ojo y del electrorretinograma, se presentaron en un alto por ciento de las portadoras afectadas. Las alteraciones oftalmológicas, perimétricas y electrorretinográficas de estos enfermos muestran las características propias de este tipo de herencia. En el estudio genético molecular del exón 15 no se encontró la mutación buscada.

Introduction: retinitis pigmentosa is an inherited disease that affects photoreceptors and pigment epithelium, causing retinal atrophy. Recessive X -linked form is the most severe in the clinical course. This disease is a health problem in our province. Objective: to characterize epidemiological and clinical genetically a family with chromosome X-linked recessive retinitis pigmentosa. Methods: a descriptive, retrospective study in 15 individuals, including seven patients and six carriers and two possibly affected, belonging to a family affected with recessive chromosome X-linked retinitis pigmentosa of Urbano Noris municipality, Holguín province was carried out. To participate in the study the patients gave their informed consent for detailed ophthalmological examination, which included visual field, retinal function and genetic study involving making tree to the fourth generation and extraction peripheral blood for DNA analysis by PCR-SSCP ORP-in exon 15 of the RPGR gene, looking for the most frequent mutation. Results the age group between 10-19 and 20-29 years predominated with 28.57 % in both cases. The age at onset was early in all patients; vitreous abnormalities predominated in 71.43 %. 42.85 % of the patients was in the final stage of the disease and had no registrable electroretinogram (71.43 %). 60 % of the carriers presented pigment pre-injury in the fundus, tapetal reflection, coinciding with subnormal electroretinograms. Conclusions: the disease onset was presented early. Vitreous features and no registrable electroretinogram alterations were the most prevailing clinical features. Most patients were in stage IV of the disease. Lesions in the fundus and electroretinograms were present in a high percentage of the affected carriers. Ophthalmic perimeter and electroretinographic alterations of these patients show the characteristics of this type of heritage features. In the molecular genetic study of exon ORP-15 the necessary mutation was not found.

Rapid detection of chromosome X, Y, 13, 18, and 21 aneuploidies by primed in situ labeling/synthesis technique.

AIMS AND OBJECTIVE: Primed in situ labeling/synthesis (PRINS) technique is an alternative to fluorescent in situ hybridization for chromosome analysis. This study was designed to evaluate the application of PRINS for rapid diagnosis of common chromosomal aneuploidy. MATERIALS AND METHODS: We have carried out PRINS using centromere specific oligonucleotide primers for chromosome X, Y, 13, 18 and 21 on lymphocyte metaphase and interphase cells spread. Specific primer was annealed in situ, followed by elongation of primer by Taq DNA polymerase in presence of labeled nucleotides. Finally, reaction was stopped and visualized directly under fluorescent microscope. RESULTS: Discrete centromere specific signals were observed with each primer. CONCLUSION: PRINS seems to be a rapid and reliable method to detect common chromosome aneuploidy in peripheral blood lymphocyte metaphase and interphase cells.

Análisis de marcadores STR sobre el cromosoma X en una población de Bogotá / STR markers analysis on X chromosome in a population from Bogotá

El análisis de marcadores del cromosoma X ha sido ampliamente usado en el área de la genética clínica, particularmente, para el análisis molecular de enfermedades ligadas al X. Recientemente, se han reconocido muchas repeticiones cortas en tándem (Short Tandem Repeats, STR) sobre este cromosoma, por su importancia en análisis forense y de paternidad. Los marcadores gonosómicos son especialmente eficientes para resolver casos difíciles, ya que las probabilidades de exclusión media son mayores que con los marcadores STR autosómicos. Objetivo. Determinar la frecuencia alélica y haplotípica de 10 marcadores STRs sobre el cromosoma X en 200 muestras de hombres no relacionados de la ciudad de Bogotá. Materiales y métodos. Se analizaron 200 muestras de sangre de hombres no emparentados nacidos en Bogotá. El ADN genómico fue extraído mediante la técnica Whatman FTA y amplificados por PCR. Los productos se analizaron en un secuenciador automático ABI Prism 310, con el software GeneMapper, versión 3.2. Resultados. Los sistemas evaluados indicaron la presencia de 6 a 11 alelos, con el mayor polimorfismo para los sistemas DXS6809 y DXS6789, seguido por el sistema DXS9902. Las frecuencias alélicas oscilaron entre 0,005 y 0,565, mientras que la frecuencia haplotípica fue de 0,005. Los parámetros forenses utilizados en este estudio reportaron que el sistema DXS7132 mostró una mayor diversidad y PD (0,832211 y 0,82805) respectivamente indicando que este sistema es altamente informativo; el sistema que presentó menor diversidad y PD fue el sistema DXS7133. Conclusión. Los diez marcadores analizados en este estudio permiten la genotipificación simultánea de los 10 STRs en solo una PCR, adicionalmente se evidenció que los marcadores analizados son ampliamente informativos y que su utilización puede ser de gran aporte en la práctica forense, particularmente en los casos de parentesco u otras deficiencias.

X chromosome markers analysis has been used widely in the clinical genetics area, particularly in molecular diseases X-linked analysis. Recently, many short tandem repeats (Short Tandem Repeats, STRs) on this chromosome has been recognized, by importance in forensic and paternity analysis. The gonosomal markers are particularly efficient resolve difficult cases, since the odds of half exclusion outweigh the STR autosomes markers. Objective. Determine the allelic frequency and haplotype frequency of 10 STRs markers located on the X chromosome, in 200 samples of unrelated men in the Bogotá city. Materials and methods. 200 blood samples were analyzed from unrelated males born in Bogotá. DNA extraction was performed using the Whatman FTA technique and PCR amplified. The products were analyzed in automatic sequencer ABI Prism 310, software GeneMapper, version 3.2. Results. The systems tested, showed of 6-11 alleles, with greater polymorphism DXS6809 and DXS6789 systems and this followed for DXS9902 system. The range of Allele frequencies from 0.005 to 0.565, while the haplotype frequency was 0.005. The forensic parameters used in this study, reported that the DXS7132 system showed greater diversity and PD (0.832211 and 0.82805) respectively, suggesting that this system is highly informative, the system had lower PD and diversity DXS7133 system. Conclusion. The ten analyzed markers in this study allow simultaneous genotyping of 10 STRs in only one PCR additionally revealed that informative markers are widely analyzed and their use can greatly contribute in forensics practice, particularly in cases of family or other deficiencies.

Falência ovariana precoce em portadores da pré-mutação do gene FMR1: revisão da literatura / Premature ovarian failure in FMR1 premutation carriers: a literature review

A mutação do gene FMR1 é um fator genético importante para a determinação multifatorial da idade da menopausa. Portadoras da pré-mutação podem ter a vida reprodutiva encurtada e devem ser alertadas sobre o risco de transmissão da Síndrome do X Frágil para seus descendentes. O objetivo deste trabalho foi mostrar dados atualizados sobre as implicações genotípica e fenotípica da pré-mutação do gene FMR1 na reprodução humana.

The FMR1 mutation is an important genetic factor in the multifactor determination of menopause age. Premutation carriers can have reproductive life shortened and should be alerted about the risk of transmitting the Fragile X Syndrome to their descendents. The purpose of this paper was to show updated data about the genotypic and phenotypic implications of FMR1 premutation on human reproduction.

Fluorescence in situ Hybridization using Chromosome X alpha-Satellite Probe To Evaluate Engraftment and To Monitor Residual Disease after Bone Marrow Transplantation / 대한임상병리학회지

BACKGROUND: Several methods have been used to evaluate the engraftment and to monitor residual disease after bone marrow transplantation (BMT). Among them, karyotyping have been useful in gauging engraftment following opposite sex BMT. More recently, fluorescence in situ hybridization (FISH) has also been applied to determine engraftment and residual status. In order to establish the utility of this method in clinical practice, we have evaluated the data from FISH and several methods. METHODS: We performed FISH using chromosome X alpha-satellite probe (Oncor , USA) on twenty eight peripheral blood and nine bone marrow nuclear cells from eleven patients who underwent sex mis-matched transplant and from a patient who had a loss of X chromosome. RESULTS: In nine patients with well engrafted BMT, signals of host cells showed less than 5% in all patients, evaluated 21-210 days post-transplant. Mixed chimerism was detected in six patients; transiently in early post-transplant period in four, in a patient with engraftment failure, and in a patient with relapse, respectively. CONCLUSION: FISH using X probe is a rapid, quantitative and sensitive 'interphase cytogenetic method' for the evaluation of engraftment and monitoring of residual disease following sex mis-matched BMT or BMT in a patient with a loss of X chromosome; It is especially useful in early post-transplant period when ony a few cells are available during severe cytopenia.