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 […]
Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders
Brain. 2023 Nov 10:awad380. doi: 10.1093/brain/awad380. Online ahead of print. ABSTRACT The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 […]
Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma
Nat Genet. 2023 Nov 9. doi: 10.1038/s41588-023-01551-3. Online ahead of print. ABSTRACT Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 […]
ARF1 prevents aberrant type I interferon induction by regulating STING activation and recycling
Nat Commun. 2023 Nov 1;14(1):6770. doi: 10.1038/s41467-023-42150-4. ABSTRACT Type I interferon (IFN) signalling is tightly controlled. Upon recognition of DNA by cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) translocates along the endoplasmic reticulum (ER)-Golgi axis to induce IFN signalling. Termination is achieved through autophagic degradation or recycling of STING by retrograde Golgi-to-ER transport. […]
NBSTRN Tools to Advance Newborn Screening Research and Support Newborn Screening Stakeholders
Int J Neonatal Screen. 2023 Oct 30;9(4):63. doi: 10.3390/ijns9040063. ABSTRACT Rapid advances in the screening, diagnosis, and treatment of genetic disorders have increased the number of conditions that can be detected through universal newborn screening (NBS). However, the addition of conditions to the Recommended Uniform Screening Panel (RUSP) and the implementation of nationwide screening has […]