A targeted gene panel that covers coding, non-coding and short tandem repeat regions improves the diagnosis of patients with neurodegenerative diseases

Genetic testing for neurodegenerative diseases (NDs) is highly challenging because of genetic heterogeneity and overlapping manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington\u27s disease and spinocerebellar ataxias type 3 (SCA3). Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known or likely pathogenic variation was found in 54 patients; 27 patients demonstrated clinical profiles that matched the variants; and 16 patients whose original diagnosis were refined. A high concordance of variant calling were observed when comparing the results from TGP and whole-exome sequencing of four patients. Our in-house STR detection algorithm has reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combined comprehensive TGPs-bioinformatics pipeline can improve the clinical diagnosis of NDs

Unexpectedly Higher Morbidity and Mortality of Hospitalized Elderly Patients Associated with Rhinovirus Compared with Influenza Virus Respiratory Tract Infection

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Discovery and genomic characterization of a novel bat sapovirus with unusual genomic features and phylogenetic position

Sapovirus is a genus of caliciviruses that are known to cause enteric disease in humans and animals. There is considerable genetic diversity among the sapoviruses, which are classified into different genogroups based on phylogenetic analysis of the full-length capsid protein sequence. While several mammalian species, including humans, pigs, minks, and dogs, have been identified as animal hosts for sapoviruses, there were no reports of sapoviruses in bats in spite of their biological diversity. In this report, we present the results of a targeted surveillance study in different bat species in Hong Kong. Five of the 321 specimens from the bat species, Hipposideros pomona, were found to be positive for sapoviruses by RT-PCR. Complete or nearly full-length genome sequences of approximately 7.7 kb in length were obtained for three strains, which showed similar organization of the genome compared to other sapoviruses. Interestingly, they possess many genomic features atypical of most sapoviruses, like high G+C content and minimal CpG suppression. Phylogenetic analysis of the viral proteins suggested that the bat sapovirus descended from an ancestral sapovirus lineage and is most closely related to the porcine sapoviruses. Codon usage analysis showed that the bat sapovirus genome has greater codon usage bias relative to other sapovirus genomes. In summary, we report the discovery and genomic characterization of the first bat calicivirus, which appears to have evolved under different conditions after early divergence from other sapovirus lineages.published_or_final_versio

Clinical and virological factors associated with viremia in pandemic influenza A/H1N1/2009 virus infection

BACKGROUND: Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance. METHODOLOGY/PRINCIPAL FINDINGS: Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples. CONCLUSION: Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein.published_or_final_versio

Human H7N9 virus induces a more pronounced pro-inflammatory cytokine but an attenuated interferon response in human bronchial epithelial cells when compared with an epidemiologically-linked chicken H7N9 virus

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Concurrent comparison of epidemiology, clinical presentation and outcome between adult patients suffering from the pandemic influenza A (H1N1) 2009 virus and the seasonal influenza A virus infection

Purpose of study: The demographics, clinical features and outcome of patients with pandemic influenza A (H1N1) 2009 infection were compared with a concurrent cohort of patients with seasonal influenza A infection. Study design: The clinical and microbiological data of hospitalised adult patients admitted between 29 June and 28 October 2009, with pandemic A (H1N1) 2009 or seasonal influenza A infection, were analysed. Results: A total of 186 patients including 69 pandemic A (H1N1) and 117 seasonal influenza were analysed. The majority (75%) under 50 years of age had pandemic A (H1N1). Compared with seasonal influenza, pandemic A (H1N1) patients were younger (median age 47 years vs 76 years, p<0.001), less likely to have lower respiratory tract symptoms (46.4% vs 66.7%, p=0.007), but more likely to be obese (5.8% vs 0%, p=0.018), pregnant (7.2% vs 0.9%, p=0.027) or have no underlying predisposing factors (24.6% vs 5.1%, p<0.001). Patients with pandemic A (H1N1) were more likely to receive oseltamivir (91.3% vs 40.2%, p<0.001), but less likely to receive antibiotics (75.4% vs 90.6%, p=0.005). Respiratory failure was the reason for intensive care unit admission for all four patients with pandemic A (H1N1), but only for one of three patients with seasonal influenza. There were no statistical significant differences in the rate of intensive care unit admission or death. Conclusions: In addition to age, several clinical parameters were different between pandemic A (H1N1) and seasonal influenza. However, since both seasonal and pandemic influenza can lead to significant morbidity and mortality, the impact of pre-existing seasonal influenza should not be underestimated during the pandemic period.published_or_final_versio

Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic

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A sensitive and specific antigen detection assay for Middle East respiratory syndrome coronavirus

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