Detecting methylation quantitative trait loci using a methylation random field method
Brief Bioinform. 2021 Aug 19:bbab323. doi: 10.1093/bib/bbab323. Online ahead of print. ABSTRACT DNA methylation may be regulated by genetic variants within a genomic region, referred to as methylation quantitative trait loci (mQTLs). The changes of methylation levels can further lead to alterations of gene expression, and influence the risk of various complex human diseases. Detecting […]
To Be or No B2: A Rare Cause of Stridor and Weakness in a Toddler
Child Neurol Open. 2021 Aug 5;8:2329048X211030723. doi: 10.1177/2329048X211030723. eCollection 2021 Jan-Dec. ABSTRACT We present a case of a young child with a rare metabolic disorder whose clinical presentation resembled that of autoimmune myasthenia gravis. The differential diagnosis was expanded when autoantibody testing was negative and the patient did not respond to standard immunomodulatory therapies. Rapid […]
Rapid whole genome sequencing in critically ill children: Shifting from unease to evidence, education and equitable implementation
J Pediatr. 2021 Aug 11:S0022-3476(21)00761-7. doi: 10.1016/j.jpeds.2021.08.006. Online ahead of print. NO ABSTRACT PMID:34390697 | DOI:10.1016/j.jpeds.2021.08.006
Developmental and temporal characteristics of clonal sperm mosaicism
Cell. 2021 Aug 7:S0092-8674(21)00883-7. doi: 10.1016/j.cell.2021.07.024. Online ahead of print. ABSTRACT Throughout development and aging, human cells accumulate mutations resulting in genomic mosaicism and genetic diversity at the cellular level. Mosaic mutations present in the gonads can affect both the individual and the offspring and subsequent generations. Here, we explore patterns and temporal stability of […]
Exome sequencing of child-parent trios with bladder exstrophy: Findings in 26 children
Am J Med Genet A. 2021 Aug 5. doi: 10.1002/ajmg.a.62439. Online ahead of print. ABSTRACT Bladder exstrophy (BE) is a rare, lower ventral midline defect with the bladder and part of the urethra exposed. The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role […]
Use of Metagenomic Next-Generation Sequencing to Identify Pathogens in Pediatric Osteoarticular Infections
Open Forum Infect Dis. 2021 Jul 17;8(7):ofab346. doi: 10.1093/ofid/ofab346. eCollection 2021 Jul. ABSTRACT BACKGROUND: Osteoarticular infections (OAIs) are frequently encountered in children. Treatment may be guided by isolation of a pathogen; however, operative cultures are often negative. Metagenomic next-generation sequencing (mNGS) allows for broad and sensitive pathogen detection that is culture-independent. We sought to evaluate […]
A human three-dimensional neural-perivascular ‘assembloid’ promotes astrocytic development and enables modeling of SARS-CoV-2 neuropathology
Nat Med. 2021 Jul 9. doi: 10.1038/s41591-021-01443-1. Online ahead of print. ABSTRACT Clinical evidence suggests the central nervous system is frequently impacted by SARS-CoV-2 infection, either directly or indirectly, although the mechanisms are unclear. Pericytes are perivascular cells within the brain that are proposed as SARS-CoV-2 infection points. Here we show that pericyte-like cells (PLCs), […]
Functional and structural analyses of novel Smith-Kingsmore Syndrome-Associated MTOR variants reveal potential new mechanisms and predictors of pathogenicity
PLoS Genet. 2021 Jul 1;17(7):e1009651. doi: 10.1371/journal.pgen.1009651. Online ahead of print. ABSTRACT Smith-Kingsmore syndrome (SKS) is a rare neurodevelopmental disorder characterized by macrocephaly/megalencephaly, developmental delay, intellectual disability, hypotonia, and seizures. It is caused by dominant missense mutations in MTOR. The pathogenicity of novel variants in MTOR in patients with neurodevelopmental disorders can be difficult to […]
Uncertain, Not Unimportant: Callosal Dysgenesis and Variants of Uncertain Significance in ROBO1
Pediatrics. 2021 Jun 30:e2020019000. doi: 10.1542/peds.2020-019000. Online ahead of print. ABSTRACT Congenital anomalies affect 3% to 5% of births and remain the leading cause of infant death in the United States. As whole exome and genome sequencing are increasingly used to diagnose underlying genetic disease, the patient’s clinical presentation remains the most important context for […]
Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish
Genet Med. 2021 Jun 25. doi: 10.1038/s41436-021-01239-1. Online ahead of print. ABSTRACT PURPOSE: Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function […]