Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Análisis de polimorfismos genéticos del receptor beta-2 adrenérgico en pacientes pediátricos asmáticos y controles sanos en una muestra de la ciudad de Bogotá

El asma bronquial es una enfermedad inflamatoria crónica, se asocia a hiperrespuesta de la vía aérea, la cual lleva a episodios recurrentes de sibilancias, tos y disnea. La entidad se ha correlacionado con una gran variedad de genes involucrados en su fisiopatología, dentro de los cuales se encuentran genes localizados en el cromosoma 5 (5q23-31), como el del Receptor ß2 Adrenérgico (RB2A). En el presente trabajo se realizó una estimación de las frecuencias de los polimorfismos Arg16Gly, Gln27Glu y Thr164Ile de este receptor, y se estudió la relación existente entre los diferentes polimorfismos y asma, así como su relación con respecto a la severidad de la enfermedad, finalmente se estimó la relación de los haplotipos conformados por estos tres polimorfismos y su asociación con la enfermedad y severidad del fenotipo asmático.Bronchial asthma is a chronic inflammatory disease, is associated with airway hyperresponsiveness, which leads to recurrent episodes of wheezing, coughing and dyspnea. The entity has been correlated with a variety of genes involved in its pathophysiology, within which are genes located on chromosome 5 (5q23-31), as the ß2 Adrenergic Receptor (RB2A). In the present study was conducted to estimate the distribution of frequencies of polymorphisms Arg16Gly, Gln27Glu and Thr164Ile of this receptor, and studied the relationship between different polymorphisms and asthma and their relation with respect to the severity of the disease, finally estimated the relationship of the haplotypes formed by these three polymorphisms and their association with disease and severity of the asthma phenotype

Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family

"Hypokalaemic periodic paralysis (HypoPP) is an autosomal dominant disorder, which is characterized by periodic attacks of muscle weakness associated with a decrease in the serum potassium level. A major disease-causing gene for HypoPP has been identified as CACNA1S, which encodes the skeletal muscle calcium channel ?-subunit with four transmembrane domains (I-IV), each with six transmembrane segments (S1-S6). To date, all CACNA1S mutations identified in HypoPP patients are located within the voltage-sensor S4 segment. In this study we report a novel CACNA1S mutation in a new region of the protein, the S3 segment of domain III. We characterized a four-generation South American family with HypoPP. Genetic analysis identified a novel V876E mutation in all HypoPP patients in the family, but not in normal family members or 160 control people. Clinical analysis indicates that mutation V876E is associated with a severe outcome as characterized by a very early age of onset, complete penetrance and a severe prognosis including death. These results identify a new mutation in CACNA1S and expand the spectrum of CACNA1S mutations associated with HypoPP. © 2009 The Japan Society of Human Genetics All rights reserved.

Ausencia del rearreglo RET/PTC1 en una muestra de sujetos colombianos con carcinoma papilar de tiroides del Hospital de San José en Bogotá: serie de casos

24 p.Introducción: El carcinoma papilar de tiroides es la neoplasia endocrina más común, se han evaluado marcadores con posible utilidad pronóstica, decidimos describir la presencia del rearreglo del RET/PTC1, tiroiditis linfocítica y características clínicas asociadas en pacientes con cáncer papilar de tiroides en el Hospital de San José de Bogotá – Colombia. Materiales y métodos: Se consultaron los registros clínicos de forma retrospectiva identificando los pacientes con tiroidectomía completa y diagnóstico de cáncer papilar. Se realizó el corte histológico, verificación del tejido tumoral; se recolectó una muestra y se ejecutó extracción de ARN. La presencia del rearreglo del gen RET/PTC1 se verificó por medio del uso de PCR en tiempo real. Resultados: Se seleccionaron 55 pacientes con cáncer papilar de tiroides, el 93 % (50/55) fueron de género femenino, edad promedio de 45,8 años. La variante histológica más frecuente fue la clásica (49 %). Se evidenció una relación entre la tiroiditis linfocítica y la cantidad de ganglios positivos en segmentos distintos al vaciamiento central, así como tiroiditis y valor de los anticuerpos antitiroideos. En las muestras analizadas no se halló expresión del rearregloRET/PTC1. Conclusiones: En este estudio no se documentó la presencia del rearregloRET/PTC1. Existió relación entre tiroiditis linfocítica y la cantidad de ganglios positivos en segmentos distintos al vaciamiento central; se debe continuar la búsqueda de marcadores que permitan diferenciar el pronóstico en este grupo de pacientes

Genotypic and allelic frequencies of apolipoprotein e (APOE) in a sample of adults in bogotá

Introducción: la apolipoproteína E (APOE) es una glicoproteína implicada en el transporte de moléculas lipídicas. Se han descrito tres alelos del gen APOE: Ɛ2, Ɛ3 y Ɛ4. Varios estudios demuestran asociación de la isoforma APOE4 con Alzheimer de inicio tardío. Objetivos: determinar las frecuencias genotípicas y alélicas del gen APOE en una muestra de adultos en Bogotá. Materiales y métodos: estudio observacional descriptivo de corte transversal. A partir de una muestra de sangre periférica se extrajo ADN genómico y se realizó PCR-Tetraprimer para la determinación de los alelos de APOE. Resultados: se incluyeron 1.254 sujetos, 942 mujeres (75%) y 312 hombres (25%) con edades entre 40 y 100 años. El alelo más frecuente fue el Ɛ3 (85%), seguido por Ɛ4 (11%) y Ɛ2 (2%). De la población que manifestó tener ascendencia cundiboyacense, 567 sujetos (74.6%) presentaban el genotipo Ɛ3/Ɛ3, mientras que 156 (20.4%) el Ɛ3/Ɛ4, 23 (3%) el Ɛ2/Ɛ3, 11 (1.5%) el Ɛ4/Ɛ4, y 4 (0.5%) el Ɛ2/Ɛ4. Los individuos con genotipo Ɛ2/Ɛ2 manifestaron no conocer el dato de ascendencia. Conclusiones: las frecuencias alélicas y genotípicas de APOE varían según el origen étnico, sin embargo es posible la identificación de sujetos con el genotipo menos frecuente (Ɛ2/Ɛ2) al analizar muestras de mayor tamaño. En los reportes previos en el país no se ha descrito el genotipo Ɛ2/Ɛ2, el cual fue identificado en la presente muestra como el de menor proporción.

Association between apoε4 allele and cardio-metabolic and social risk factors with cognitive impairment in elderly population from Bogota

Ser um portador ϵ4 no gene Apoϵ tem sido sugerido como um fator modificador da interação entre fatores cardiometabólicos, de risco social e o desenvolvimento de comprometimento cognitivo. Objetivo: O objetivo principal deste trabalho é avaliar a existência de tal interação em uma amostra da população idosa de Bogotá. Métodos: Um estudo transversal foi realizado com 1.263 indivíduos com mais de 50 anos. Cada participante foi diagnosticado por consenso após avaliações neuropsicológicas e neuropsiquiátricas, sob um diagnóstico de cognição normal, comprometimento cognitivo leve de acordo com os critérios de Petersen ou demência de acordo com os critérios do Manual Diagnóstico e Estatístico de Trastornos Mentais (DSM-IV). Apoϵ4 foi tipificada e uma análise do Montréal Cognitive Assessment Test (teste de MoCA) foi realizada em cada grupo portador ou não do alelo ϵ4. Resultados: Nosso estudo mostrou que 75% eram mulheres com idade mediana de 68 anos (intervalo interquartil 62 a 74 anos) e escolaridade mediana de seis anos (intervalo interquartil 4 a 12 anos). A demência estava relacionada ao baixo nível de escolaridade ≤5 anos Odds Ratio (OR)=11,20 (intervalo de confiança — IC95% 4,99–25,12), pressão alta OR=1,45 (IC95% 1,03–2,05) e idade acima de 70 anos OR=7,68 (IC95% 3,49–16,90), independentemente de ser ou não portador do alelo ϵ4. Indivíduos diabéticos com demência portadores do alelo ϵ4 mostraram tendência de exibir pontuações mais baixas no teste MoCA quando comparados com indivíduos diabéticos com demência não portadores do alelo ϵ4. Conclusões: A presença do alelo ϵ4 não modifica a relação entre o comprometimento cognitivo e os diferentes fatores de risco cardiometabólico e social, exceto em diabéticos portadores de ϵ4 com demência, que exibiram tendência a apresentar menores escores no teste MoCA quando comparados com indivíduos diabéticos com demência não portadores do alelo ϵ4.Being an ϵ4 carrier in the Apoϵ gene has been suggested as a modifying factor for the interaction between cardio-metabolic, social risk factors, and the development of cognitive impairment. Objective: The main objective of this study was to assess the existence of such interaction in a sample of Bogota’s elderly population. Methods: A cross-sectional study was conducted with 1,263 subjects older than 50 years. Each participant was diagnosed by consensus, after neuropsychological and neuropsychiatric evaluations, under a diagnosis of normal cognition, mild cognitive impairment (MCI) according to Petersen’s criteria, or dementia according to DSM-IV criteria. Apoϵ was typified and an analysis of MoCA test was performed in each group carrying or not ϵ4 allele. Results: Our study showed that 75% were women with a median age of 68 years (interquartile range 62–74 years) and a median schooling for 6 years (interquartile range 4–12 years). Dementia was related to low education level of ≤5 years OR=11.20 (95%CI 4.99–25.12), high blood pressure (HBP) OR=1.45 (95%CI 1.03–2.05), and age over 70 years OR=7.68 (95%CI 3.49–16.90), independently of being or not an ϵ4 allele carrier. Diabetic subjects with dementia carrying ϵ4 allele showed a tendency to exhibit lower scores on the MoCA test, when compared with noncarriers’ diabetic subjects with dementia. Conclusions: The presence of ϵ4 allele does not modify the relationship between cognitive impairment and the different cardio-metabolic and social risk factors, except in diabetic subjects ϵ4 carriers with dementia who showed a tendency to exhibit lower scores of the MoCA test, when compared with noncarriers’ diabetic subjects with dementia

Molecular Tumor Board Improves Outcomes for Hispanic Patients With Advanced Solid Tumors

PURPOSEMultidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in developing countries. Herein, we describe the possible benefits and limitations of the first MTB established in Colombia.METHODSDemographic, clinical, and genomic information was collected between August 2020 and November 2021. By mid-2020, an MTB strategy was created to discuss clinical cases with one or more genomic alterations identified by next-generation sequencing using an open-access virtual platform. We characterized the patient population as benefiting from the recommended treatment option. We assessed the benefits and access to available targeted therapies that have the potential to change clinical management by making recommendations to treating oncologists on the basis of genomic profiling. However, we did not assess the treatment oncologists' compliance with MTB recommendations because they were not intended to replace clinical judgment/standard of care.RESULTSA total of 146 patients were included in the discussions of the MTB. The median age was 59 years, and 59.6% were women. Genomic results prompting a change in therapeutic decisions were obtained in 53.1% of patients (95% CI, 44.9 to 61.3). The most prevalent malignancy was non–small-cell lung cancer (51%). Other malignancies represented 60%, 50%, and 30% of patients with soft-tissue sarcomas, brain tumors, and breast cancer, respectively.CONCLUSIONUsing an open-access virtual platform, MTBs were feasible in low- and middle-income countries on the basis of the capability to provide the benefits and access to available targeted therapies that are not standard of care. Furthermore, MTB recommendations were made available to the treating oncologist in different locations across Colombia, providing the option to modify clinical management in most of these patients