DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62 % similar overall (28 % identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-lik

Teste ergométrico e o Holter de 24 horas na detecção de arritmias ventriculares complexas em diferentes estádios da cardiopatia chagásica crônica Exercise testing and 24 hours Holter monitoring in the detection of complex ventricular arrhythmias in different stages of chronic Chagas' heart disease

Comparou-se o teste ergométrico com Holter de 24 horas na detecção de arritmias ventriculares complexas em diferentes estádios da cardiopatia chagásica crônica. Avaliados 71 pacientes sem outras doenças associadas, idade=51±10,3, metade mulheres. Divididos em quatro grupos conforme o grau de acometimento cardíaco. A estatística esta discriminada no corpo do trabalho. Ao Holter, no grupo IA as arritmias ventriculares complexas foram detectadas em 4,3%, IB em 25%, II em 55% e no grupo III em 90%. Nos grupos II e III não houve diferença entre os exames na detecção de arritmias ventriculares complexas (p=NS). Nos grupos IA e IB, houve uma concordância de 100% no teste ergométrico na não detecção de arritmias ventriculares complexas entre dois observadores. No grupo II, a concordância foi de 70% (kappa=0,368, p=0,003) e de 90% (kappa=0,78, p=0,002) no grupo III. Foi observado diferenças na presença de arritmias ventriculares complexas entre os pacientes dos grupos em fase inicial e avançada da cardiopatia chagásica crônica. Nos pacientes dos grupos II e III não houve diferença entre os dois exames na detecção das arritmias ventriculares complexas. Pacientes dos grupos IA e IB é razoável indicar Holter e/ou o teste ergométrico na ocorrência de progressão da doença.<br>To detect complex ventricular arrhythmias in different stages of chronic chagasic cardiopathy, the results of exercise testing to 24 hours Holter monitoring have been compared. We evaluated a group of 71 patients, half women, aged 51±10.3, with no others associated diseases. These patients were separated in 4 groups according to degree of cardiac involvement. Statistical data can be found elsewhere in the study. In group IA, Holter monitoring detected 4.3% of complex ventricular arrhythmias, group IB 25%, group II 55% and group III 90%. We found no difference between Holter and exercise testing in the detection of complex ventricular arrhythmias in groups II and III (p = ns). In groups IA and IB we found 100% concordance, concerning the no detection of complex ventricular arrhythmias by exercise testing seen by two independent examiners. In group II there was a 70% concordance (kappa=0.368, p=0.003) and 90% in group III (kappa=0.78, p=0.002). Different results were found, concerning the presence of complex ventricular arrhythmias, among patients in the initial and advanced stages of chronic chagasic cardiopathy. In groups II and III we found no difference between the two methods in the detection of complex ventricular arrhythmias. It seems reasonable to recommend either Holter on exercise testing in groups IA and IB if progression of disease is noticed