RESUMEN
A 'Down Syndrome critical region' (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6-8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS.
Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Síndrome de Down/genética , Trisomía/genética , Mapeo Cromosómico , Cromosomas Humanos Par 21/genética , Síndrome de Down/patología , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Trisomía/patologíaRESUMEN
Acute bronchiolitis represents the leading cause of hospitalization in infants. Together with a respiratory syncytial virus, rhinovirus (RV) is one of the most common pathogens associated with bronchiolitis, and its genetic diversity (>150 types) makes the recurrence of RV infections each year quite typical. The frequency of RV infection and co-infection with other viruses and its impact on the clinical course of bronchiolitis have been studied by several authors with controversial results. Some studies demonstrate that multiple virus infections result in more severe clinical presentation and a higher risk of complications, whereas other studies suggest no influence on clinical course. Moreover, RV bronchiolitis has been reported to potentially contribute to the development of long-term sequelae, such as recurrent wheezing and asthma, in the pediatric population. In the present review, we summarize the most recent findings of the role of RV infection in children with acute bronchiolitis, its impact on subsequent asthma development, and the implication in clinical practice.
RESUMEN
Respiratory syncytial virus (RSV) is the main cause of acute respiratory tract infections in infants and it also induces significant disease in the elderly. The clinical course may be severe, especially in high-risk populations (infants and elderly), with a large number of deaths in developing countries and of intensive care hospitalizations worldwide. To date, prevention strategies against RSV infection is based on hygienic measures and passive immunization with humanized monoclonal antibodies, limited to selected high-risk children due to their high costs. The development of a safe and effective vaccine is a global health need and an important objective of research in this field. A growing number of RSV vaccine candidates in different formats (particle-based vaccines, vector-based vaccines, subunit vaccines and live-attenuated vaccines) are being developed and are now at different stages, many of them already being in the clinical stage. While waiting for commercially available safe and effective vaccines, immune prophylaxis in selected groups of high-risk populations is still mandatory. This review summarizes the state-of-the-art of the RSV vaccine research and its implications for clinical practice, focusing on the characteristics of the vaccines that reached the clinical stage of development.