RESUMO
Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues.
Assuntos
Predisposição Genética para Doença/genética , Deficiência Intelectual/genética , Proteína 2 de Ligação a Metil-CpG/genética , Mutação de Sentido Incorreto , Adolescente , Adulto , Sequência de Aminoácidos , Sítios de Ligação/genética , Análise Mutacional de DNA/métodos , Feminino , Humanos , Deficiência Intelectual/patologia , Masculino , Fenótipo , Síndrome de Rett/genética , Síndrome de Rett/patologia , Homologia de Sequência de AminoácidosRESUMO
The aim of this study was to predict the clinical efficacy of different antimicrobials in the treatment of patients with acute otitis media (AOM), before and after the change in the proportion of middle ear pathogens observed after the introduction of the new conjugated heptavalent penumococcal vaccine (pPCV-7). The therapeutic Outcomes model was used to predict the likelihood of clinical success. According to this mathematical model the obtained rank order of predicted clinical efficacy was similar in the pre-PVC7 period and the post-PVC period. The results suggest that ceftriaxone and amoxicillin/clavulanate are the antibiotics with the highest predicted clinical efficacy, whereas cefaclor, azithromycin, erythromycin and clarithromycin are those with the lowest predicted clinical efficacy. The differences between antibiotics with good and those with low antibacterial activity were greater when only cases of bacterial AOM were considered. Antibiotics for which the highest clinical efficacy was predicted should maximize the likelihood of cure in outpatient antibiotic treatment of AOM.
