Multi-center implementation of rapid whole genome sequencing provides additional evidence of its utility in the pediatric inpatient setting
Front Pediatr. 2024 Feb 19;12:1349519. doi: 10.3389/fped.2024.1349519. eCollection 2024. ABSTRACT OBJECTIVE: Multi-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease. STUDY DESIGN: rWGS tests were ordered at eight hospitals between November […]
Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations
bioRxiv [Preprint]. 2024 Feb 16:2024.02.13.580158. doi: 10.1101/2024.02.13.580158. ABSTRACT Genomics for rare disease diagnosis has advanced at a rapid pace due to our ability to perform “N-of-1” analyses on individual patients. The increasing sizes of ultra-rare, “N-of-1” disease cohorts internationally newly enables cohort-wide analyses for new discoveries, but well-calibrated statistical genetics approaches for jointly analyzing these […]
Loss of symmetric cell division of apical neural progenitors drives DENND5A -related developmental and epileptic encephalopathy
medRxiv. 2024 Jan 31:2022.08.23.22278845. doi: 10.1101/2022.08.23.22278845. Preprint. ABSTRACT Developmental and epileptic encephalopathies (DEEs) are a heterogenous group of epilepsies in which altered brain development leads to developmental delay and seizures, with the epileptic activity further negatively impacting neurodevelopment. Identifying the underlying cause of DEEs is essential for progress toward precision therapies. Here we describe a […]
The Plasma Lipidomic Landscape in Patients with Sepsis due to Community-acquired Pneumonia
Am J Respir Crit Care Med. 2024 Jan 19. doi: 10.1164/rccm.202308-1321OC. Online ahead of print. ABSTRACT RATIONALE: The plasma lipidome has the potential to reflect many facets of the host status during severe infection. Previous work is limited to specific lipid groups, or focused on lipids as prognosticators. OBJECTIVES: To map the plasma lipidome during […]
The clinical and genetic landscape of developmental and epileptic encephalopathies in Egyptian children
Clin Genet. 2024 Jan 14. doi: 10.1111/cge.14481. Online ahead of print. ABSTRACT Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of epilepsies characterized by early-onset, refractory seizures associated with developmental regression or impairment, with a heterogeneous genetic landscape including genes implicated in various pathways and mechanisms. We retrospectively studied the clinical and genetic data […]
Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes
Brain. 2023 Dec 1:awad403. doi: 10.1093/brain/awad403. Online ahead of print. ABSTRACT AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with […]
Sunflower Syndrome: A Survey of Provider Awareness and Management Preferences
Pediatr Neurol. 2023 Nov 30;152:177-183. doi: 10.1016/j.pediatrneurol.2023.11.013. Online ahead of print. ABSTRACT BACKGROUND: Sunflower syndrome is a rare photosensitive pediatric epilepsy characterized by stereotyped hand-waving in response to bright lights. These stereotyped movements with maintained awareness can be mistaken for a movement disorder. This study assessed neurology providers’ diagnostic reasoning, evaluation, and treatment of Sunflower […]
Genomic data resources of the Brain Somatic Mosaicism Network for neuropsychiatric diseases
Sci Data. 2023 Nov 20;10(1):813. doi: 10.1038/s41597-023-02645-7. ABSTRACT Somatic mosaicism is defined as an occurrence of two or more populations of cells having genomic sequences differing at given loci in an individual who is derived from a single zygote. It is a characteristic of multicellular organisms that plays a crucial role in normal development and […]
Spliceosome malfunction causes neurodevelopmental disorders with overlapping features
J Clin Invest. 2023 Nov 14:e171235. doi: 10.1172/JCI171235. Online ahead of print. ABSTRACT Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), […]
Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome
Am J Hum Genet. 2023 Nov 13:S0002-9297(23)00366-X. doi: 10.1016/j.ajhg.2023.10.013. Online ahead of print. ABSTRACT Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WW domain-binding protein 4 (WBP4) is part of the early spliceosomal complex and has not been previously associated with human pathologies in the Online Mendelian Inheritance […]