Introduction: Increased bacterial translocation and alterations to gut microbiota composition have been described in HIV infection and contribute to immune activation and inflammation. These effects persist despite combined antiretroviral therapy (cART). However, the contribution of different cART combinations has not yet been investigated. The aim of this study was to analyse the long-term effects of different combinations of cART on bacterial translocation and gut microbiota composition in HIV-infected patients. Methods: We carried out a cross-sectional study of 45 HIV-infected patients on cART, classified as nucleoside reverse transcriptase inhibitors (NRTIs)+ protease inhibitors (PIs) (n = 15), NRTIs+ non-nucleoside reverse transcriptase inhibitors (NNRTIs) (n = 22), and NRTIs+ integrase strand transfer inhibitors (INSTIs) (n = 8). Untreated HIV-infected patients (n = 5) and non-infected volunteers (n = 21) were also included. Soluble markers of bacterial translocation and inflammation were measured and gut microbiota composition was analysed using 16S rDNA pyrosequencing (Illumina MiSeq). Results: The NRTIs+INSTIs regimen was associated with levels of systemic inflammation that were similar to uninfected controls. The reduction in faecal bacterial diversity induced by HIV infection was also restored by this regimen. HIV infection was more closely related to changes in lower taxonomic units and diversity rather than at the phylum level. The NRTIs+PIs regimen showed the highest reduction in bacterial species, whereas NRTIs+INSTIs induced a minor loss of bacterial species and a significant increase in others. Conclusions: Our study demonstrated that INSTI-based ART was associated with levels of systemic inflammation and microbial diversity similar to that of uninfected controls. The role of INSTIs other than raltegravir needs to be further investigated. Patients on the NRTIs+PIs regimen presented the highest reduction in bacterial species compared with other antiretrovirals and naive patients. Thus, different cART regimens are associated with diverse profiles in gut microbiota composition. Longitudinal and functional studies are needed to better understand these findings.

Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and a FMR1 testing as first-tier tests, but there is increasing evidence that support the use of NGS for the diagnosis of NDDs. Specifically in ASD, it has not been extensively evaluated and, thus, we performed and compared the clinical utility of CMA, FMR1 testing, and/or whole exome sequencing (WES) in a cohort of 343 ASD patients. We achieved a global diagnostic rate of 12.8% (44/343), the majority of them being characterised by WES (33/44; 75%) compared to CMA (9/44; 20.4%) or FMR1 testing (2/44; 4.5%). Taking into account the age at which genetic testing was carried out, we identified a causal genetic alteration in 22.5% (37/164) of patients over 5 years old, but only in 3.9% (7/179) of patients under this age. Our data evidence the higher diagnostic power of WES compared to CMA in the study of ASD and support the implementation of WES as a first-tier test for the genetic diagnosis of this disorder, when there is no suspicion of fragile X syndrome.

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A subset of families with co-dominant or recessive inheritance has been described in several genes previously associated with dominant inheritance. Those recessive families displayed similar, more severe, or even completely different phenotypes to their dominant counterparts. We report the first patients harboring homozygous disease-related variants in three genes that were previously associated with dominant inheritance: a loss-of-function variant in the CACNA1A gene and two missense variants in the RET and SLC20A2 genes, respectively. All patients presented with a more severe clinical phenotype than the corresponding typical dominant form. We suggest that co-dominant or recessive inheritance for these three genes could explain the phenotypic differences from those documented in their cognate dominant phenotypes. Our results reinforce that geneticists should be aware of the possible different forms of inheritance in genes when WES variant interpretation is performed. We also evidence the need to refine phenotypes and inheritance patterns associated with genes in order to avoid failures during WES analysis and thus, raising the WES diagnostic capacity in the benefit of patients.

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