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Exome sequencing has enabled molecular diagnoses for rare disease patients but often with initial diagnostic rates of ~25-30%. Here we develop a robust computational pipeline to rank variants for reassessment of unsolved rare disease patients. A comprehensive web-based patient report is generated in which all deleterious variants can be filtered by gene, variant characteristics, OMIM disease and Phenolyzer scores, and all are annotated with an ACMG classification and links to ClinVar.

At the end of a 60-day course of narrowband UVB phototherapy, administered to individuals with early multiple sclerosis, there were changes in the relative proportions of circulating B-cell subsets. This study investigated phototherapy-associated changes to cytokine responses of B cells when exposed to a TLR7 ligand.

Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding.

Multidrug-resistant tuberculosis (MDR-TB) is a major global public health concern. However, there is a dearth of literature on whether MDR-TB and its medications impact maternal and perinatal outcomes, and when such evidence exists the findings are conflicting. This systematic review and meta-analysis aimed to examine the impact of MDR-TB and its medications during pregnancy on maternal and perinatal outcomes.

The risk of entry to state care during infancy is increasing, both here in England and abroad, with most entering within a week of birth ('newborns'). However, little is known about these infants or of their pathways through care over early childhood.

Sensitive measures of early lung disease are being integrated into therapeutic trials and clinical practice in cystic fibrosis (CF). The impact of early disease surveillance (EDS) using these novel and often intensive techniques on young children and their families is not well researched.

ClC-7 is a chloride-proton antiporter of the CLC protein family. In complex with its accessory protein Ostm-1, ClC-7 localizes to lysosomes and to the osteoclasts' ruffled border, where it plays a critical role in acidifying the resorption lacuna during bone resorption. Gene inactivation in mice causes severe osteopetrosis, neurodegeneration, and lysosomal storage disease. Mutations in the human CLCN7 gene are associated with diverse forms of osteopetrosis.

Background: β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE. Objective: We sought to identify genetic predisposing factors for immediate reactions to β-lactam antibiotics.

Scabies is an important predisposing factor for impetigo but its role in more serious skin and soft tissue infections (SSTIs) is not well understood. Information is limited on incidence of SSTIs in the presence of endemic scabies. We conducted a prospective study of hospital admissions for SSTIs in the Northern Division of Fiji (population: 131,914). Prospective surveillance for admissions with impetigo, abscess, cellulitis, wound infection, pyomyositis, necrotizing fasciitis, infected scabies, and crusted scabies was conducted at the Division's referral hospital between 2018 to 2019. Information was collected on demographic characteristics, clinical features, microbiology, treatment and outcomes.

Rett syndrome (RTT) is a rare neurodevelopmental disorder mainly affecting females and is caused by a mutation in the MECP2 gene. Recent research identified the domains of quality of life (QOL) important for children with RTT but there has been no investigation of domains important for adults. This qualitative study explored QOL in adults with RTT and compared domains with those previously identified for children.