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 […]
Use of Plasma Metagenomic Next-generation Sequencing for Pathogen Identification in Pediatric Endocarditis
Pediatr Infect Dis J. 2020 Dec 30;Publish Ahead of Print. doi: 10.1097/INF.0000000000003038. Online ahead of print. ABSTRACT Pediatric infective endocarditis incurs significant morbidity and generally occurs among children with underlying heart disease. Identification of a pathogen is critical in determining appropriate therapy. However, standard diagnostic testing has limited sensitivity. We describe a case series of […]
Expanding the phenotype of PIGS-associated early onset epileptic developmental encephalopathy
Epilepsia. 2021 Feb;62(2):e35-e41. doi: 10.1111/epi.16801. Epub 2021 Jan 7. ABSTRACT The phosphatidylinositol glycan anchor biosynthesis class S protein (PIGS) gene has recently been implicated in a novel congenital disorder of glycosylation resulting in autosomal recessive inherited glycosylphosphatidylinositol-anchored protein (GPI-AP) deficiency. Previous studies described seven patients with biallelic variants in the PIGS gene, of whom two […]
The nucleotide prodrug CERC-913 improves mtDNA content in primary hepatocytes from DGUOK-deficient rats
J Inherit Metab Dis. 2021 Mar;44(2):492-501. doi: 10.1002/jimd.12354. Epub 2021 Jan 15. ABSTRACT Loss-of-function mutations in the deoxyguanosine kinase (DGUOK) gene result in a mitochondrial DNA (mtDNA) depletion syndrome. DGUOK plays an important role in converting deoxyribonucleosides to deoxyribonucleoside monophosphates via the salvage pathway for mtDNA synthesis. DGUOK deficiency manifests predominantly in the liver; the […]
An online compendium of treatable genetic disorders
Am J Med Genet C Semin Med Genet. 2021 Mar;187(1):48-54. doi: 10.1002/ajmg.c.31874. Epub 2020 Dec 22. ABSTRACT More than 4,000 genes have been associated with recognizable Mendelian/monogenic diseases. When faced with a new diagnosis of a rare genetic disorder, health care providers increasingly turn to internet resources for information to understand the disease and direct […]
UBR7 functions with UBR5 in the Notch signaling pathway and is involved in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism
Am J Hum Genet. 2021 Jan 7;108(1):134-147. doi: 10.1016/j.ajhg.2020.11.018. Epub 2020 Dec 18. ABSTRACT The ubiquitin-proteasome system facilitates the degradation of unstable or damaged proteins. UBR1-7, which are members of hundreds of E3 ubiquitin ligases, recognize and regulate the half-life of specific proteins on the basis of their N-terminal sequences (“N-end rule”). In seven individuals […]
De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy
Genet Med. 2020 Dec 10. doi: 10.1038/s41436-020-01020-w. Online ahead of print. ABSTRACT PURPOSE: This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. METHODS: Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through […]
Metagenomic sequencing and evaluation of the host response in the pediatric aerodigestive population
Pediatr Pulmonol. 2021 Feb;56(2):516-524. doi: 10.1002/ppul.25198. Epub 2020 Dec 14. ABSTRACT OBJECTIVES: To assess the diagnostic utility of metagenomic sequencing in pediatric aerodigestive clinic patients being evaluated for chronic aspiration. We hypothesize that using a metagenomics platform will aid in the identification of microbes not found on standard culture. STUDY DESIGN AND METHODS: Twenty-four children […]