A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis
Cell. 2025 Dec 4:S0092-8674(25)01310-8. doi: 10.1016/j.cell.2025.11.014. Online ahead of print. ABSTRACT Ferroptosis, driven by uncontrolled peroxidation of membrane phospholipids, is distinct from other cell death modalities because it lacks an initiating signal and is surveilled by endogenous antioxidant defenses. Glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, although its membrane-protective function remains poorly understood. […]
Genome x Environment analysis of Sudden Unexpected Infant Death unveils etiologic heterogeneity and strong cannabis and genetic disease risks
medRxiv [Preprint]. 2025 Nov 28:2025.11.26.25341098. doi: 10.1101/2025.11.26.25341098. ABSTRACT Sudden Unexpected Infant Death (SUID), the third leading cause of infant death, has increasing incidence and multifactorial etiology. Identification of preventative interventions has hitherto been hindered by etiologic studies limited to genetic or environmental effects in isolation. Here we report a multifactorial genome x environment analysis of […]
Expanding the Phenotype of Syndromic SLC30A9-Associated Disease
Am J Med Genet A. 2025 Nov 26:e70007. doi: 10.1002/ajmga.70007. Online ahead of print. ABSTRACT SLC30A9 mutations are linked to Birk-Landau-Perez syndrome, which is characterized by neurodevelopmental and renal disease, thought to result from impaired zinc homeostasis. In this report, we describe a patient with a homozygous likely pathogenic SLC30A9 variant with atypical chorio-retinal degeneration, […]
Clinical utility and cost-effectiveness of BeginNGS newborn screening by genome sequencing and standard newborn screening for severe childhood genetic diseases: an adaptive, international and comparative clinical trial
BMJ Open. 2025 Nov 13;15(11):e098609. doi: 10.1136/bmjopen-2024-098609. ABSTRACT INTRODUCTION: In the last 60 years, newborn bloodspot screening (NBS) has expanded as a public health intervention from a single severe childhood genetic disease (SCGD) to up to as many as 80 SCGD and testing of ~40 million newborns/year worldwide. However, the gap between current NBS and […]
A phenotypic brain organoid atlas and biobank for neurodevelopmental disorders
Cell Stem Cell. 2025 Nov 3:S1934-5909(25)00374-1. doi: 10.1016/j.stem.2025.10.006. Online ahead of print. ABSTRACT Thousands of genes are associated with neurodevelopmental disorders (NDDs), yet mechanisms and targeted treatments remain elusive. To fill these gaps, we present a California Institute of Regenerative Medicine (CIRM)-initiated NDD biobank of 352 publicly available genetically diverse patient-derived induced pluripotent stem cells […]
Rapid Genome Sequencing Compared with a Gene Panel in Critically Ill Infants with a Suspected Genetic Disorder: An Economic Evaluation
J Pediatr. 2025 Oct 31:114889. doi: 10.1016/j.jpeds.2025.114889. Online ahead of print. ABSTRACT OBJECTIVE: To compare 1-year healthcare costs and quality-adjusted life years (QALYs) for two diagnostic strategies in critically ill infants with suspected genetic disorders: 1) early rapid genome sequencing (within 7 days of admission) for all infants, and 2) early targeted neonatal gene sequencing […]
Splicing and frameshift variants in QSER1 may be involved in developmental phenotypes
HGG Adv. 2025 Oct 25:100539. doi: 10.1016/j.xhgg.2025.100539. Online ahead of print. ABSTRACT Human development is a complex process that requires precise control of gene expression through regulatory proteins. Recently, heterozygous variants in PRR12, encoding a proline-rich regulatory protein, were found to cause a variable phenotype involving developmental delay/cognitive impairment, neuropsychiatric diagnoses, structural eye anomalies, congenital […]
Sequencing Analysis Demonstrates That a Complex Genetic Architecture Contributes to Risk for Spina Bifida
Birth Defects Res. 2025 Oct;117(10):e2533. doi: 10.1002/bdr2.2533. ABSTRACT BACKGROUND: Spina bifida (SB), a common neural tube defects (NTDs), has a complex genetic architecture that remains incompletely understood. Although prior studies have identified rare, deleterious single nucleotide variants (SNVs) in SB, broader contributions to risk remain unclear. Here, we investigated shared genetic risk among 256 SB […]
ACTB deletions or single-nucleotide loss-of-function variants: expansion and further delineation of the phenotype and review of the literature
J Med Genet. 2025 Oct 8:jmg-2025-110631. doi: 10.1136/jmg-2025-110631. Online ahead of print. ABSTRACT BACKGROUND: Pathogenic gain-of-function or dominant-negative effect missense variations in ACTB are associated with a neurodevelopmental disorder characterised by intellectual disability (ID), seizures, sensorineural hearing loss, cerebral, renal and ocular abnormalities and dysmorphic features (Baraitser-Winter cerebrofrontofacial syndrome). ACTB encodes beta-actin, a highly conserved […]
Clinical Genetic Testing in Schizophrenia: A Systematic Review and Meta-Analysis
Biol Psychiatry. 2025 Sep 30:S0006-3223(25)01485-4. doi: 10.1016/j.biopsych.2025.09.010. Online ahead of print. ABSTRACT BACKGROUND: Genetic testing may provide important diagnostic information for individuals with schizophrenia, but the frequency with which clinically significant variants are identified across different testing approaches has not been systematically evaluated. METHODS: We conducted a systematic review and meta-analysis searching MEDLINE, EMBASE, and […]