202 results match your criteria: "Genomic Medicine Center[Affiliation]"
Retina
October 2023
Singapore National Eye Centre, Singapore Eye Research Institute, and the Ophthalmology and Visual Sciences Academic Clinical Program (EYE ACP), Duke-NUS Graduate Medical School, Singapore.
Purpose: The study aimed to describe the phenotypic features of retinitis pigmentosa (RP) associated with the previously described EYS C2139Y variant in Singaporeans and establish the importance of this variant as a prevalent cause of RP among East Asians.
Methods: A clinical phenotyping and exome-sequencing study was conducted on consecutive patients with nonsyndromic RP. Epidemiological analysis was performed using Singaporean and global population-based genetic data.
Acta Oncol
June 2023
Dept of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
JCO Precis Oncol
June 2023
Section of Clinical Genetics, Pathology and Molecular Diagnostics, Medical Services, Region Skåne, University Hospital, SE-22185, Lund, Sweden.
Am J Bioeth
July 2023
Children's Mercy - Kansas City.
Front Oncol
June 2023
Department of Medicine, Division of Clinical Epidemiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Introduction: Analyzing liquid biopsies for tumor-specific aberrations can facilitate detection of measurable residual disease (MRD) during treatment and at follow-up. In this study, we assessed the clinical potential of using whole-genome sequencing (WGS) of lymphomas at diagnosis to identify patient-specific structural (SVs) and single nucleotide variants (SNVs) to enable longitudinal, multi-targeted droplet digital PCR analysis (ddPCR) of cell-free DNA (cfDNA).
Methods: In 9 patients with B-cell lymphoma (diffuse large B-cell lymphoma and follicular lymphoma), comprehensive genomic profiling at diagnosis was performed by 30X WGS of paired tumor and normal specimens.
PLoS Genet
June 2023
Program in Molecular Medicine, University of Massachusetts Chan Medical School, Biotech II, Worcester, Massachusetts, United States of America.
Motile and non-motile cilia play critical roles in mammalian development and health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). In mammals, malfunction of non-motile cilia due to IFT dysfunction results in complex developmental phenotypes that affect most organs.
View Article and Find Full Text PDFChild Neurol Open
May 2023
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
pathogenic variants in have recently been reported as a novel genetic cause of leukoencephalopathy. Here, we describe a male individual who presented in the first year of life with clinical features resembling Pelizaeus-Merzbacher disease (PMD), including nystagmus, hypotonia, and global developmental delay, and which later progressed to include ataxia and spasticity. Brain MRI at the age of two revealed diffuse hypomyelination.
View Article and Find Full Text PDFNat Commun
May 2023
Department of Pediatrics, Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO, USA.
Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.
View Article and Find Full Text PDFCell Genom
May 2023
Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan.
Influenza A virus (IAV) infections are frequent every year and result in a range of disease severity. Here, we wanted to explore the potential contribution of transposable elements (TEs) to the variable human immune response. Transcriptome profiling in monocyte-derived macrophages from 39 individuals following IAV infection revealed significant inter-individual variation in viral load post-infection.
View Article and Find Full Text PDFCell Genom
May 2023
Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
Commun Biol
May 2023
Genomic Medicine Center, Children's Mercy Research Institute, Children's Mercy Kansas City, Kansas City, MO, 64108, USA.
Human milk is essential for infant nutrition and immunity, providing protection against infections and other immune-mediated diseases during the lactation period and beyond in later childhood. Milk contains a broad range of bioactive factors such as nutrients, hormones, enzymes, immunoglobulins, growth factors, cytokines, and antimicrobial factors, as well as heterogeneous populations of maternal cells. The soluble and cellular components of milk are dynamic over time to meet the needs of the growing infant.
View Article and Find Full Text PDFJ Med Genet
October 2023
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
Pediatr Neurol
July 2023
Department of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, Missouri; Genomic Medicine Center, Children's Mercy Research Institute, Kansas City, Missouri; University of Missouri Kansas City, School of Medicine, Kansas City, Missouri. Electronic address:
Eur Heart J
July 2023
Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK.
This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation.
View Article and Find Full Text PDFFront Genet
April 2023
Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy.
Sci Rep
April 2023
Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Whole genome sequencing (WGS) has the potential to be a comprehensive genetic test, especially relevant for individuals with neurodevelopmental disorders, syndromes and congenital malformations. However, the cost consequences of using whole genome sequencing as a first-line genetic test for these individuals are not well understood. The study objective was to compare the healthcare costs and diagnostic yield when WGS is performed as the first-line test instead of chromosomal microarray analysis (CMA).
View Article and Find Full Text PDFJ Clin Lipidol
June 2023
Department of Medicine, University of California San Diego, Room 1081, 9500 Gilman Drive, La Jolla, CA 92093 USA (Drs Joseph L. Witztum; Sotirios Tsimikas); Ionis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92010, USA (Drs Veronica J. Alexander; Lynnetta Watts; Shuting Xia; Sotirios Tsimikas).
Background: Familial chylomicronemia syndrome (FCS) is a rare, autosomal recessive genetic disorder characterized by a marked increase in plasma triglyceride (TG) levels and recurrent episodes of pancreatitis. The response to conventional TG-lowering therapies is suboptimal. Volanesorsen, an antisense oligonucleotide that targets hepatic apoC-III mRNA, has been shown to significantly reduce TGs in patients with FCS.
View Article and Find Full Text PDFJACC Adv
May 2023
Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, Québec, Canada.
Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). Untreated patients present with extensive xanthomas and premature atherosclerosis. Lipid-lowering therapy is highly efficacious and has dramatically increased life expectancy of patients with HoFH.
View Article and Find Full Text PDFJ Clin Invest
June 2023
Division of Neonatology, Department of Pediatrics.
Neonatal herpes simplex virus (HSV) infection is a devastating disease with substantial morbidity and mortality. The genetic basis of susceptibility to HSV in neonates remains undefined. We evaluated a male infant with neonatal skin/eye/mouth (SEM) HSV-1 disease, who had complete recovery after acyclovir but developed HSV-1 encephalitis at 1 year of age.
View Article and Find Full Text PDFFront Neurol
April 2023
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Introduction: Rare neurodevelopmental disorders, including inherited white matter disorders or leukodystrophies, often present a diagnostic challenge on a genetic level given the large number of causal genes associated with a range of disease subtypes. This study aims to demonstrate the challenges and lessons learned in the genetic investigations of leukodystrophies through presentation of a series of cases solved using exome or genome sequencing.
Methods: Each of the six patients had a leukodystrophy associated with hypomyelination or delayed myelination on MRI, and inconclusive clinical diagnostic genetic testing results.
Am J Hum Genet
May 2023
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:
Heterozygous pathogenic variants in POLR1A, which encodes the largest subunit of RNA Polymerase I, were previously identified as the cause of acrofacial dysostosis, Cincinnati-type. The predominant phenotypes observed in the cohort of 3 individuals were craniofacial anomalies reminiscent of Treacher Collins syndrome. We subsequently identified 17 additional individuals with 12 unique heterozygous variants in POLR1A and observed numerous additional phenotypes including neurodevelopmental abnormalities and structural cardiac defects, in combination with highly prevalent craniofacial anomalies and variable limb defects.
View Article and Find Full Text PDFGenet Med
July 2023
Department of Human Genetics, Inselspital Bern, University of Bern, Bern, Switzerland; Department for Biomedical Research, University of Bern, Bern, Switzerland; Bern Center for Precision Medicine (BCPM), University of Bern, Bern, Switzerland. Electronic address:
Purpose: LHX2 encodes the LIM homeobox 2 transcription factor (LHX2), which is highly expressed in brain and well conserved across species, but it has not been clearly linked to neurodevelopmental disorders (NDDs) to date.
Methods: Through international collaboration, we identified 19 individuals from 18 families with variable neurodevelopmental phenotypes, carrying a small chromosomal deletion, likely gene-disrupting or missense variants in LHX2. Functional consequences of missense variants were investigated in cellular systems.
Brain
August 2023
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic ATP1A3 variants produce several distinct neurological syndromes, yet the molecular basis for phenotypic variability is unclear. We report a novel recurrent variant, ATP1A3(NM_152296.
View Article and Find Full Text PDFHypertension
June 2023
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA (M.K., X.L., X.W., H.M., Y.H., L.Q.).
Background: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life.
Methods: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. We defined the regional DNAm levels as the average methylation level of 5'-cytosine-phosphate-guanine-3' within 500 bp of (cg01820192), (cg00508575), and (cg12593793), respectively.
J Pediatr Urol
June 2023
Department of Women's and Children's Health, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Laboratory of Tissue Engineering Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Pediatric Surgery, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address:
Precision Medicine holds promise for helping us manage specific phenotypes of common diseases. For rare diseases such as hypospadias, DSD, and pediatric solid tumors, it can also reveal underlying risk factors and pathogenesis. Professors Ann Nordgren and Anna Lindstrand share their experiences in the development and ongoing initiatives of the Swedish national project on Precision Medicine and how it could change the care of pediatric urology patients.
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