202 results match your criteria: "Genomic Medicine Center[Affiliation]"

RETINITIS PIGMENTOSA ASSOCIATED WITH THE EYS C2139Y VARIANT : An Important Cause of Blindness in East Asian Populations.

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.

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Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer.

JCO Precis Oncol

June 2023

Section of Clinical Genetics, Pathology and Molecular Diagnostics, Medical Services, Region Skåne, University Hospital, SE-22185, Lund, Sweden.

Article Synopsis
  • The study examined how whole-genome sequencing (WGS) and RNA sequencing can help in diagnosing and treating childhood cancers, focusing on children with primary or relapsed solid tumors in Sweden.
  • Over the first 14 months, 118 tumors were analyzed, and 95% of those with mutations had clear clinical relevance, with significant findings such as additional subclassifications and potential treatment targets in 26% of the cases.
  • Overall, the research highlights the importance of integrating genomic data into clinical decision-making for improved diagnosis and treatment options in pediatric solid tumors.
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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.

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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.

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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.

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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.

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Transposable elements are associated with the variable response to influenza infection.

Cell 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.

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Article Synopsis
  • Researchers studied how genetic variations, particularly mobile element insertions (MEIs), affect the epigenome, especially in immune responses to influenza infection.
  • By sequencing the epigenome of macrophages from 35 diverse individuals, they discovered new epigenomic signals, revealing 2.3%-3% novel peaks in key chromatin markers.
  • The use of genome graphs helped identify 375 polymorphic MEIs in an active state, including one that changed its chromatin state post-infection and was linked to a gene that regulates influenza virus replication.
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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.

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Article Synopsis
  • RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is a genetic disorder leading to neurological issues, dental problems, and hormonal deficiencies, caused by mutations in specific genes.
  • A study evaluated the craniofacial features of 31 POLR3-HLD patients, revealing common abnormalities like a flat midface, smooth philtrum, and pointed chin, with different features linked to specific gene mutations.
  • The findings highlight that craniofacial abnormalities are prevalent in POLR3-HLD, offering detailed insights into the dysmorphic traits associated with the various genetic variants involved.
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Pseudo-Dystonia and Marked Intrafamilial Variability in CADM3-Related Disease.

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:

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2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

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.

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Editorial: Inherited and acquired ribosomopathies: missing puzzle pieces.

Front Genet

April 2023

Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), Alma Mater Studiorum University of Bologna, Bologna, Italy.

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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).

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Volanesorsen and triglyceride levels in familial chylomicronemia syndrome: Long-term efficacy and safety data from patients in an open-label extension trial.

J 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.

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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.

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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.

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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.

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POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies.

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.

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LHX2 haploinsufficiency causes a variable neurodevelopmental disorder.

Genet 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.

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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.

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DNA Methylation of Birthweight-Blood Pressure Genes and Changes of Blood Pressure in Response to Weight-Loss Diets in the POUNDS Lost Trial.

Hypertension

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.

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Precision medicine and rare diseases in pediatric urology.

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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