X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Measurement of differential cross-sections of a top quark produced in association with a W boson at √s=13 TeV with ATLAS

The differential cross-section for the production of a W boson in association with a top quark is measured for several particle-level observables. The measurements are performed using 36.1fb−1 of pp collision data collected with the ATLAS detector at the LHC in 2015 and 2016. Differential cross-sections are measured in a fiducial phase space defined by the presence of two charged leptons and exactly one jet matched to a b-hadron, and are normalised with the fiducial cross-section. Results are found to be in good agreement with predictions from several Monte Carlo event generators

Search for scalar resonances decaying into μ⁺μ⁻ in events with and without b-tagged jets produced in proton-proton collisions at √s=13 TeV with the ATLAS detector

This work is licensed under a Creative Commons Attribution 4.0 International License.A search for a narrow scalar resonance decaying into an opposite-sign muon pair produced in events with and without b-tagged jets is presented in this paper. The search uses 36.1 fb−1 of √=13 TeV proton-proton collision data recorded by the ATLAS experiment at the LHC. No significant excess of events above the expected Standard Model background is observed in the investigated mass range of 0.2 to 1.0 TeV. The observed upper limits at 95% confidence level on the cross section times branching ratio for b-quark associated production and gluon-gluon fusion are between 1.9 and 41 fb and 1.6 and 44 fb respectively, which is consistent with expectations

Distrofia miotónica tipo 1: 13 años de experiencia en un hospital terciario. Estudio clínico y epidemiológico. Correlación genotipo-fenotipo

Resumen: Introducción: Se desconoce la incidencia de la distrofia miotónica tipo 1 (DM1), enfermedad con gran variedad fenotípica, en nuestra región. El objetivo de nuestro trabajo es estimar la incidencia de DM1 en nuestro centro (referencia en Aragón) e identificar las características propias de nuestra población (correlación genotipo-fenotipo). Métodos: Estudio descriptivo retrospectivo de 459 pacientes clasificados según número de repeticiones CTG en: normal (5-35), premutado (36-50), protomutado (51-80), pequeñas expansiones (81-150), intermedias (151-1.000) y grandes (> 1.000). Además, según el fenotipo mostrado, se categorizaron como: no afectos (5-50 CTG), forma leve o asintomática (51-150 CTG), clásica (151-1.000 CTG) y severa (> 1.000 CTG). Resultados: La incidencia de DM1 fue de 20,61 (IC 95%: 19,59-21,63) casos por millón de individuos-año. Se evidenció una correlación inversa entre el número de CTG y la edad al diagnóstico genético (ρ = −0,547; IC 95%: −0,610 a −0,375; p  1000). Furthermore, according to clinical phenotype, patients were categorised as unaffected (5-50 CTG repeats), mild form or asymptomatic (51-150), classical form (151-1000), and severe form (> 1000). Results: The incidence of DM1 was 20.61 cases per million person-years (95% CI: 19.59-21.63). An inverse correlation was observed between the number of CTG repeats and the age at genetic diagnosis (ρ = −0.547; 95% CI: −0.610 to −0.375; P < .001). CTG5 was the most frequent polymorphic allele in healthy individuals. Of all patients with DM1, 28.3% presented the mild or asymptomatic form, 59.1% the classical form, and 12.6% the severe form. Inheritance was maternal in 35.1% of cases, paternal in 59.4%, and uncertain in 5.5%. In mild forms, frontal balding in men was the most prevalent phenotypic trait, as well as myotonia and cataracts, while in the classical form, ptosis, facial weakness, voice and pronunciation alterations, myotonia, and fatigue/sleepiness were most frequent. Conclusions: The incidence of DM1 in Aragon is significant. Multidisciplinary study of the phenotype of patients with DM1 is key to early diagnosis and personalised management