Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections

Open Forum Infect Dis. 2021 Mar 6;8(6):ofab104. doi: 10.1093/ofid/ofab104. eCollection 2021 Jun. ABSTRACT BACKGROUND: Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management and in characterizing prognosis. Usual care testing by culture and polymerase chain reaction is often […]

Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach

PLoS Genet. 2021 Mar 8;17(3):e1009413. doi: 10.1371/journal.pgen.1009413. eCollection 2021 Mar. ABSTRACT Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined […]

Novel Variant Findings and Challenges Associated With the Clinical Integration of Genomic Testing: An Interim Report of the Genomic Medicine for Ill Neonates and Infants (GEMINI) Study

JAMA Pediatr. 2021 Feb 15:e205906. doi: 10.1001/jamapediatrics.2020.5906. Online ahead of print. ABSTRACT IMPORTANCE: A targeted genomic sequencing platform focused on diseases presenting in the first year of life may minimize financial and ethical challenges associated with rapid whole-genomic sequencing. OBJECTIVE: To report interim variants and associated interpretations of an ongoing study comparing rapid whole-genomic sequencing […]

Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration

Sci Rep. 2021 Feb 11;11(1):3639. doi: 10.1038/s41598-021-83058-7. ABSTRACT Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in […]

Emergence of an early SARS-CoV-2 epidemic in the United States

medRxiv [Preprint]. 2021 Feb 8:2021.02.05.21251235. doi: 10.1101/2021.02.05.21251235. PMID: 33564781; PMCID: PMC7872376. Abstract The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the […]

Capsule carbohydrate structure determines virulence in Acinetobacter baumannii

PLoS Pathog. 2021 Feb 2;17(2):e1009291. doi: 10.1371/journal.ppat.1009291. eCollection 2021 Feb. ABSTRACT Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation in the capsule […]

A Case of UDP-Galactose 4′-Epimerase Deficiency Associated with Dyshematopoiesis and Atrioventricular Valve Malformations: An Exceptional Clinical Phenotype Explained by Altered N-Glycosylation with Relative Preservation of the Leloir Pathway

Mol Syndromol. 2020 Dec;11(5-6):320-329. doi: 10.1159/000511343. Epub 2020 Oct 29. ABSTRACT The generalized form of UDP-galactose-4′-epimerase (GALE) deficiency causes hypotonia, failure to thrive, cataracts, and liver failure. Individuals with non-generalized forms may remain asymptomatic with uncertain long-term outcomes. We report a 2-year-old child compound heterozygous for GALE p.R51W/p.G237D who never developed symptoms of classic galactosemia […]

Brain MR patterns in inherited disorders of monoamine neurotransmitters: An analysis of 70 patients

J Inherit Metab Dis. 2021 Jan 14. doi: 10.1002/jimd.12360. Online ahead of print. ABSTRACT Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand […]

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