Individuals with monoallelic pathogenic variants in the histone lysine methyltransferase DOT1L display global developmental delay and varying congenital anomalies. However, the impact of monoallelic loss of remains unclear. Here, we present a largely female cohort of 11 individuals with variants with developmental delays and dysmorphic facial features.
View Article and Find Full Text PDFBackground: While research has led to significant advancements in the health and life expectancy of children with Down Syndrome (DS), there remains a significant burden of disease and health inequity. Further research, focused on areas of greatest need, is imperative to address this. An understanding of what research has been undertaken, and any existing gaps, helps to guide future academic efforts.
View Article and Find Full Text PDFBackground: The UK 100,000 Genomes Project was a transformational research project which facilitated whole genome sequencing (WGS) diagnostics for rare diseases. We evaluated experiences of introducing WGS in Northern Ireland, providing recommendations for future projects. Methods: This formative evaluation included (1) an appraisal of the logistics of implementing and delivering WGS, (2) a survey of participant self-reported views and experiences, (3) semi-structured interviews with healthcare staff as key informants who were involved in the delivery of WGS and (4) a workshop discussion about interprofessional collaboration with respect to molecular diagnostics.
View Article and Find Full Text PDFPurpose: Neurodevelopmental disorders (NDDs) encompass a spectrum of genetically heterogeneous disorders with features that commonly include developmental delay, intellectual disability, and autism spectrum disorders. We sought to delineate the molecular and phenotypic spectrum of a novel neurodevelopmental disorder caused by variants in the GNAI1 gene.
Methods: Through large cohort trio-based exome sequencing and international data-sharing, we identified 24 unrelated individuals with NDD phenotypes and a variant in GNAI1, which encodes the inhibitory Gαi1 subunit of heterotrimeric G-proteins.
Purpose: Lamins are the major component of nuclear lamina, maintaining structural integrity of the nucleus. Lamin A/C variants are well established to cause a spectrum of disorders ranging from myopathies to progeria, termed laminopathies. Phenotypes resulting from variants in LMNB1 and LMNB2 have been much less clearly defined.
View Article and Find Full Text PDFObjective: The objective of this study was to evaluate the presenting features of bone and joint infections with a view to identify distinguishing trends that will be useful for pediatric emergency departments.
Methods: We performed a retrospective review of patient records over a 12-year period in the pediatric emergency department of a large regional pediatric teaching center serving a diverse population.
Results: There were 88 cases of osteoarticular infections during the study period.
Background: There is a growing body of evidence associating financial strain (FS) with poor health but most of this research has been cross-sectional and adult-focused. During the 'Great Recession' many UK households experienced increased FS. The primary aim of this study was to determine the impact of increased FS on child health.
View Article and Find Full Text PDFIntroduction: During the recent "Great Recession," many families in the United Kingdom experienced increased financial strain (FS). The aim of this study was to determine if increases in FS, occurring over the period of the "Great Recession," were associated with increased risks of persistent and relapsed tobacco use among parents.
Methods: We analyzed the Millennium Cohort Study, a longitudinal study of 18819 children born in the United Kingdom between 2000 and 2002.
Ariel is a mouse mutant that suffers from skeletal muscle myofibrillar degeneration due to the rapid accumulation of large intracellular protein aggregates. This fulminant disease is caused by an ENU-induced recessive mutation resulting in an L342Q change within the motor domain of the skeletal muscle myosin protein MYH4 (MyHC IIb). Although normal at birth, homozygous mice develop hindlimb paralysis from Day 13, consistent with the timing of the switch from developmental to adult myosin isoforms in mice.
View Article and Find Full Text PDFMyofibrillar myopathies are a heterogeneous group of neuromuscular disorders characterized by disintegration of myofibrils. The inheritance pattern is commonly autosomal dominant, but there has been a striking absence of secondary cases noted in a BAG3-associated subtype. We studied three families with BAG3 p.
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