Browsing by Author "Marques, C."
Now showing 1 - 8 of 8
Results Per Page
Sort Options
- Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 genePublication . Correia, C.; Coutinho, A.M.; Diogo, L.; Grazina, M.; Marques, C.; Miguel, T.; Ataíde, A.; Almeida, J.; Borges, L.; Oliveira, C.; Oliveira, G.; Vicente, A.M.In the present study we confirm the previously reported high frequency of biochemical markers of mitochondrial dysfunction, namely hyperlactacidemia and increased lactate/pyruvate ratio, in a significant fraction of 210 autistic patients. We further examine the involvement of the mitochondrial aspartate/glutamate carrier gene (SLC25A12) in mitochondrial dysfunction associated with autism. We found no evidence of association of the SLC25A12 gene with lactate and lactate/pyruvate distributions or with autism in 241 nuclear families with one affected individual. We conclude that while mitochondrial dysfunction may be one of the most common medical conditions associated with autism, variation at the SLC25A12 gene does not explain the high frequency of mitochondrial dysfunction markers and is not associated with autism in this sample of autistic patients.
- Detection of Anaplasma phagocytophilum, Candidatus Neoehrlichia sp., Coxiella burnetii and Rickettsia spp. in questing ticks from a recreational park, PortugalPublication . Santos, A.S.; de Bruin, A.; Veloso, A.R.; Marques, C.; Pereira da Fonseca, I.; De Sousa, R.; Sprong, H.; Santos-Silva, M.M.Tick-borne agents with medical relevance have been recorded in Portugal but little is known about their oc-currence in urban outdoor leisure areas. This study aimed to investigate ticks and tick-borne agents in threepublic parks of Lisbon’s metropolitan area. A total of 234 questing ticks belonging to eight species were found inParque Florestal de Monsanto (PFM). Ixodes ventalloi represented 40% of collections. Mitochondrial genesconfirmed Ixodes morphological identification, evidencing the intraspecific variability of I. ricinus and particu-larly I. frontalis populations. Regarding tick-borne agents, Rickettsia massiliae DNA were found in 21 (9.0%) ticks,Coxiella burnetii in 15 (6.4%), Anaplasma phagocytophilum in five (2.1%), an agent closely related to CandidatusNeoehrlichia mikurensis in two (0.9%), Rickettsia sibirica mongolitimonae and Rickettsia monacensis each in one(0.4%). Active enzootic cycles were suggested for these agents by the detection of positives in different timeperiods. Five tick species were founded with C. burnetii, including I. ventalloi which seems to be a new associationrecord. This tick was also the only species found positive for A. phagocytophilum and the Candidatus Neoehrlichiamikurensis-like agent. Two A. phagocytophilum variants were detected in PFM, one of them representing a po-tentially new ecotype already found in I. ventalloi from another Portuguese area. To the authors´ knowledge, thisis also the first report of such a Candidatus Neoehrlichia mikurensis-like microorganism. These data show aninteresting diversity of ticks and tick-borne agents with potential public health relevance in PFM, an urbanrecreational area commonly frequented by humans and their pets.
- Epidemiology of autism spectrum disorder in Portugal: prevalence, clinical characterization, and medical conditionsPublication . Oliveira, G.; Ataíde, A.; Marques, C.; Miguel, T.S.; Coutinho, A.M.; Mota-Vieira, L.; Gonçalves, E.; Lopes, N.M.; Rodrigues, V.; Carmona da Mota, H.; Vicente, A.M.The objective of this study was to estimate the prevalence of autistic spectrum disorder (ASD) and identify its clinical characterization, and medical conditions in a paediatric population in Portugal. A school survey was conducted in elementary schools, targeting 332,808 school-aged children in the mainland and 10,910 in the Azores islands. Referred children were directly assessed using the Diagnostic and Statistical Manual of Mental Disorders (4th edn), the Autism Diagnostic Interview-Revised, and the Childhood Autism Rating Scale. Clinical history and a laboratory investigation was performed. In parallel, a systematic multi-source search of children known to have autism was carried out in a restricted region. The global prevalence of ASD per 10,000 was 9.2 in mainland, and 15.6 in the Azores, with intriguing regional differences. A diversity of associated medical conditions was documented in 20%, with an unexpectedly high rate of mitochondrial respiratory chain disorders.
- Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levelsPublication . Coutinho, A.M.; Sousa, I.; Martins, M.; Correia, C.; Morgadinho, T.; Bento, C.; Marques, C.; Ataíde, A.; Miguel, T.S.; Moore, J.H.; Oliveira, G.; Vicente, A.M.Autism is a neurodevelopmental disorder of unclear etiology. The consistent finding of platelet hyperserotonemia in a proportion of patients and its heritability within affected families suggest that genes involved in the serotonin system play a role in this disorder. The role in autism etiology of seven candidate genes in the serotonin metabolic and neurotransmission pathways and mapping to autism linkage regions (SLC6A4, HTR1A, HTR1D, HTR2A, HTR5A, TPH1 and ITGB3) was analyzed in a sample of 186 nuclear families. The impact of interactions among these genes in autism was assessed using the multifactor-dimensionality reduction (MDR) method in 186 patients and 181 controls. We further evaluated whether the effect of specific gene variants or gene interactions associated with autism etiology might be mediated by their influence on serotonin levels, using the quantitative transmission disequilibrium test (QTDT) and the restricted partition method (RPM), in a sample of 109 autistic children. We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010). In addition to the previously reported contribution of SLC6A4, we found significant associations of ITGB3 haplotypes with serotonin level distribution (P = 0.0163). The most significant models contributing to serotonin distribution were found for interactions between TPH1 rs4537731 and SLC6A4 haplotypes (P = 0.002) and between HTR1D rs6300 and SLC6A4 haplotypes (P = 0.013). In addition to the significant independent effects, evidence for interaction between SLC6A4 and ITGB3 markers was also found. The overall results implicate SLC6A4 and ITGB3 gene interactions in autism etiology and in serotonin level determination, providing evidence for a common underlying genetic mechanism and a molecular explanation for the association of platelet hyperserotonemia with autism.
- Guidelines for the Detection of Rickettsia spp.Publication . Portillo, A.; de Sousa, R.; Santibánez, S.; Duarte, A.; Edouard, S.; Fonseca, I.P.; Marques, C.; Novakova, M.; Palomar, A.M.; Santos, M.; Silaghi, C.; Tomassone, L.; Zúquete, S.; Oteo, J.A.The genus Rickettsia (Rickettsiales: Rickettsiaceae) includes Gram-negative, small, obligate intracellular, nonmotile, pleomorphic coccobacilli bacteria transmitted by arthropods. Some of them cause human and probably also animal disease (life threatening in some patients). In these guidelines, we give clinical practice advices (microscopy, serology, molecular tools, and culture) for the microbiological study of these microorganisms in clinical samples. Since in our environment rickettsioses are mainly transmitted by ticks, practical information for the identification of these arthropods and for the study of Rickettsia infections in ticks has also been added.
- Ixodes ventalloi: a vector role to be exploredPublication . Santos, A.S.; de Bruin, A.; Veloso, R.; Marques, C.; Pereira da Fonseca, I.; de Sousa, R.; Sprong, H.; Santos-Silva, M.M.Ixodes ventalloi is still a poorly studied tick and its public health relevance largely unknown. In Portugal it is known to share habitats with Ixodes ricinus in mainland littoral areas and to parasitize a variety of wild and domesticated animals and also humans. The potential involvement of I. ventalloi in the natural cycle of tick‐borne agents was first suggested by the detection of a new variant of Anaplasma phagocytophilum in questing and cat‐feeding ticks from Setúbal and Santarém, and is again questioned here. In this study we present the detection of A. phagocytophilum, Candidatus Neoehrlichia mikurensis and Coxiella burnetii in questing I. ventalloi collected from Parque Florestal de Monsanto (PFM), a Lisbon recreational park.
- MECP2 coding sequence and 3'UTR variation in 172 unrelated autistic patientsPublication . Coutinho, A.M.; Oliveira, G.; Katz, C.; Feng, J.; Yan, J.; Yang, C.; Marques, C.; Ataíde, A.; Miguel, T.S.; Borges, L.; Almeida, J.; Correia, C.; Currais, A.; Bento, C.; Mota-Vieira, L.; Temudo, T.; Santos, M.; Maciel, P.; Sommer, S.S.; Vicente, A.M.Mutations in the coding sequence of the methyl-CpG-binding protein 2 gene (MECP2), which cause Rett syndrome (RTT), have been found in male and female autistic subjects without, however, a causal relation having unequivocally been established. In this study, the MECP2 gene was scanned in a Portuguese autistic population, hypothesizing that the phenotypic spectrum of mutations extends beyond the traditional diagnosis of RTT and X-linked mental retardation, leading to a non-lethal phenotype in male autistic patients. The coding region, exon-intron boundaries, and the whole 3'UTR were scanned in 172 patients and 143 controls, by Detection of Virtually All Mutations-SSCP (DOVAM-S). Exon 1 was sequenced in 103 patients. We report 15 novel variants, not found in controls: one missense, two intronic, and 12 in the 3'UTR (seven in conserved nucleotides). The novel missense change, c.617G > C (p.G206A), was present in one autistic male with severe mental retardation and absence of language, and segregates in his maternal family. This change is located in a highly conserved residue within a region involved in an alternative transcriptional repression pathway, and likely alters the secondary structure of the MeCP2 protein. It is therefore plausible that it leads to a functional modification of MeCP2. MECP2 mRNA levels measured in four patients with 3'UTR conserved changes were below the control range, suggesting an alteration in the stability of the transcripts. Our results suggest that MECP2 can play a role in autism etiology, although very rarely, supporting the notion that MECP2 mutations underlie several neurodevelopmental disorders.
- Overview on canine vector-borne diseases agents transmitted by ticks in PortugalPublication . Da Fonseca, I.P.; Marques, C.; Duarte, A.; Leal, A.; Meireles, J.; Santos-Silva, M.M.; Santos, A.S.