A novel single nucleotide polymorphism assay for the detection of N501Y SARS-CoV-2 variants.

The N501Y mutation in SARS-CoV-2 variants found in several strains from the UK, South Africa and Brazil has been linked to increased transmission. In order to discriminate N501Y variants quickly, a single nucleotide polymorphism (SNP) discrimination assay was designed and validated. It was then deployed prospectively in 757 nasopharyngeal swabs. Validation of the novel variant discrimination assay corroborated the results in all validation panel samples (n = 63) through sequencing. This novel variant discrimination assay was then deployed prospectively in 757 clinical nasopharyngeal swabs during the last week of January 2021. N501Y was found in 206 (27.4 %) of the samples: 94 (28.2 %) men and 112 (26.85 %) women (p = 0.73). The patients in whom it was identified had a mean age of 47.8 ± 25.8 (0-96) years, similar to that of patients without this variant: 51.7 ± 25.9 (0-104) years (p = 0.06). 501Y variant was confirmed in 34 samples by sequence method and 501 N wild type was confirmed in 67. This method is sensitive, specific, and simple to apply in any microbiology lab.

Homeostasis del magnesio. Etiopatogenia, clínica y tratamiento de la hipomagnesemia. A propósito de un caso / No disponible

El magnesio es el catión extracelular más abundante en el cuerpo humano y el segundo más abundante intracelular después del potasio. Es esencial para la transferencia, almacenamiento y utilización de la energía como regulador y catalizador de más de 300 sistemas enzimáticos. La hipomagnesemia puede producir una variedad de anormalidades metabólicas y consecuencias clínicas. Puede resultar del desequilibrio entre la absorción intestinal y la excreción renal. La principal consecuencia relacionada directamente con la hipomagnesemia son las arritmias cardiovasculares por hipopotasemia secundaria, y si no se reconoce y trata puede ser fatal. En este artículo revisamos las hipomagnesemias haciendo hincapié en los mecanismos moleculares responsables de la homeostasis del magnesio, diagnóstico diferencial y tratamiento, a propósito de la descripción de las manifestaciones clínicas y bioquímicas y el defecto genético en una familia afectada de síndrome de Gitelman (AU)

Magnesium is the fourth-most abundantion in the human body and the second-most abundant intracellular cation after potassium. Magnesium is pivotal in the transfer, storage, and utilization of energy as it regulates and catalyzes more than300 enzyme systems. Hypomagnesemia may thus result in avariety of metabolic abnormalities and clinical consequences. It results from an imbalance between gastrointestinal absorption and renal excretion of magnesium. The main consequence related directly to hypomagnesemia is cardiovascular arrhythmias secondary to hipokaliemia and if this is not recognized and treated it may be fatal. In this article we review the hypomagnesemic disorders in children with emphasis on the molecular mechanisms responsible for abnormalities in magnesium homeostasis, differential diagnosis and appropriate therapy, and we describe the clinical and biochemical manifestations as well as the genetic defect in a family with Gitelman syndrome (AU)

Nefronoptisis y enfermedad quística medular: aspectos genéticos / No disponible

No disponible

Avances en la genética molecular de las enfermedades de la infancia / Advances in molecular genetics of childhood diseases

No disponible

Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene.

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chronic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a case-control study. We genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the same geographic area. The observed difference in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0.05) was found by considering the recessive hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency; however, it was protective in men regarding the recessive hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele distribution was similar among the 46 thrombophilic patients (antithrombin, protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men.

[Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHRF) genotype]. / Reducción de concentraciones elevadas de homocisteína con ácido fólico y vitaminas B en pacientes con tromboembolia venosa: relación entre respuesta y genotipo C677T de la metilén tetrahidrofólico reductasa (MTHFR).

BACKGROUND: High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It essentially depends on the nutritional status of folic acid (FA) and vitamins B12 or B6, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype. PATIENTS AND METHODS: 227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut-off point (men = 16, women = 15 mumol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B12 and 100 mg of B6, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response. RESULTS: The mean fasting tHcy was 12.3 mumol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) mumol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 mumol/l (37%) (n = 18), the C/T from 25.0 to 12.6 mumol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 mumol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = -0.471) (p = 0.005) was observed between age and response. CONCLUSIONS: The FA/B6/B12 based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.

[20210A mutation of the prothrombin and venous thromboembolism gene]. / Mutacion 20210A del gen de la protrombina y tromboembolismo venoso.

PURPOSE: Various genetic disorders interact with environmental factors to cause thrombotic diseases. Recently, a G to A transition at nucleotide 20210 in the prothrombin gene, has been described in association with venous thromboembolism, in Dutch population. Currently, several reports want to know the frequence of this mutation in other ethnic groups and populations. The aim of this work was to assess the prevalence rates of prothrombin mutation in both, thrombotic and healthy Spanish populations, and to estimate the associated relative risks. We described the clinical features in our series of thrombotic carriers and moreover, we compared a routine clotting test versus DNA analysis in the diagnosis of this anomaly. POPULATION, MATERIAL AND METHODS: The design was a non-matched case-control study. The involved populations were: 187 patients of venous thromboembolic diseases and 200 healthy controls. Patients and controls were genotyped and both, carriers and non-carrier patients, were analyzed by a routine prothrombin clotting assay, to determine the sensibility and specificity and optimal cut off level of the test. RESULTS: The 20210 A allele was identified in 17 patients (9.1%) and in 7 controls (3.5%), with a 2.76-fold increased risk (OR 2.76, 95% CI = 1.12-6.81), in carriers. One patient and none of the controls were homozygous. The clinical characteristics (first manifestation age or thrombotic recurrence) are similar in both, carriers and non-carriers, patient groups. The prothrombin level by a routine coagulometric method was 1.31 +/- 0.14 U/ml (95% CI = 1.24-1.38) for the 20210 A carriers, whereas for the non carrier-patients was significantly lower, 1.06 (95% CI = 1.03-1.08) (p < 0.00001). With a cut off level of 1.25 U/ml, 12/16 (75%) carriers and 14/132 (10.6%) non-carriers were positive. Therefore, the sensibility was 75% and the specificity 89.4%. With a cut off level of 1.40 U/ml the diagnostic efficiency was even worse. CONCLUSIONS: 3.5% of healthy subjects and 9.1% of thromboembolic patients carried this prothrombin mutation with a relative risk of 2.76 (95% CI = 1.12-6.81). The relevant clinical features are similar to the rest of the series. The mean prothrombin level was higher (1.31 U/ml) than in the normal patients (1.06 U/ml), but the clotting test seems inappropriate for a diagnostic purpose.

A patient homozygous for mutation 20210A in the prothrombin gene with venous thrombosis and transient ischemic attacks of thrombotic origin.

It is well established that genetic disorders interact with environmental factors to cause thrombotic diseases. Therefore, antithrombin, protein C, protein S deficiencies and the more recently described factor V Leiden and prothrombin mutations are currently been investigated to explain some thrombophilic states. We report the case of a 63-year-old man who developed two transient ischemic attacks and two years later an extensive femoro-iliac venous thrombosis. He was genotyped as FV R506Q negative and FII G20210A positive in homozygous state (FII 20210AA).