Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations
Nat Commun. 2025 Aug 7;16(1):7267. doi: 10.1038/s41467-025-61712-2. ABSTRACT Genomics for rare disease diagnosis has advanced at a rapid pace due to our ability to perform in-depth analyses on individual patients with ultra-rare diseases. The increasing sizes of ultra-rare disease cohorts internationally newly enables cohort-wide analyses for new discoveries, but well-calibrated statistical genetics approaches for jointly […]
Extrachromosomal DNA-Driven Oncogene Dosage Heterogeneity Promotes Rapid Adaptation to Therapy in MYCN-Amplified Cancers
Cancer Discov. 2025 Aug 7:OF1-OF24. doi: 10.1158/2159-8290.CD-24-1738. Online ahead of print. ABSTRACT Extrachromosomal DNA (ecDNA) amplification enhances intercellular oncogene dosage variability and accelerates tumor evolution by violating foundational principles of genetic inheritance through its asymmetric mitotic segregation. Spotlighting high-risk neuroblastoma, we demonstrate how ecDNA amplification undermines the clinical efficacy of current therapies in cancers with […]
Long Term Follow Up of Children Who Received Rapid Genomic Sequencing
Genet Med. 2025 Mar 7:101403. doi: 10.1016/j.gim.2025.101403. Online ahead of print. ABSTRACT PURPOSE: To explore long-term trajectories of children who received rapid genome sequencing (RGS) in intensive care settings. METHODS: We examined the electronic health records (EHR) of 67 critically ill pediatric patients who received RGS six to eight years ago with a collective initial […]
MPSE identifies newborns for whole genome sequencing within 48 h of NICU admission
NPJ Genom Med. 2025 Jun 12;10(1):47. doi: 10.1038/s41525-025-00506-3. ABSTRACT Identifying critically ill newborns who will benefit from whole genome sequencing (WGS) is difficult and time-consuming due to complex eligibility criteria and evolving clinical features. The Mendelian Phenotype Search Engine (MPSE) automates the prioritization of neonatal intensive care unit (NICU) patients for WGS. Using clinical data […]
Advancing precision care in pregnancy through a treatable fetal findings list
Am J Hum Genet. 2025 Apr 3:S0002-9297(25)00110-7. doi: 10.1016/j.ajhg.2025.03.011. Online ahead of print. ABSTRACT The use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade. Fetal GS also offers an opportunity to identify incidental genomic variants that are unrelated to the fetal phenotype but may […]
The contribution of de novo coding mutations to meningomyelocele
Nature. 2025 Mar 26. doi: 10.1038/s41586-025-08676-x. Online ahead of print. ABSTRACT Meningomyelocele (also known as spina bifida) is considered to be a genetically complex disease resulting from a failure of the neural tube to close. Individuals with meningomyelocele display neuromotor disability and frequent hydrocephalus, requiring ventricular shunting. A few genes have been proposed to contribute […]
Prefrontal cortex modulation of stress by primary cilia
Neuron. 2025 Apr 16;113(8):1126-1128. doi: 10.1016/j.neuron.2025.03.026. ABSTRACT In this issue of Neuron, Yang et al.1 reveal that primary cilia in mouse prefrontal cortex excitatory neurons regulate stress responses via cAMP/PKA signaling. Stress induces ciliary elongation, enhancing corticosterone-mediated neuronal inhibition. Cilia loss reduces stress sensitivity, highlighting their role in stress adaptation, with potential therapeutic relevance. PMID:40245842 […]
A machine learning decision support tool optimizes WGS utilization in a neonatal intensive care unit
NPJ Digit Med. 2025 Jan 30;8(1):72. doi: 10.1038/s41746-025-01458-9. ABSTRACT The Mendelian Phenotype Search Engine (MPSE), a clinical decision support tool using Natural Language Processing and Machine Learning, helped neonatologists expedite decisions to whole genome sequencing (WGS) to diagnose patients in the neonatal intensive care unit. After the MPSE was introduced, utilization of WGS increased, time […]
A comparative view of human and mouse telencephalon inhibitory neuron development
Development. 2025 Jan 1;152(1):dev204306. doi: 10.1242/dev.204306. Epub 2025 Jan 2. ABSTRACT Human GABAergic inhibitory neurons (INs) in the telencephalon play crucial roles in modulating neural circuits, generating cortical oscillations, and maintaining the balance between excitation and inhibition. The major IN subtypes are based on their gene expression profiles, morphological diversity and circuit-specific functions. Although previous […]
Genome-based newborn screening for severe childhood genetic diseases has high positive predictive value and sensitivity in a NICU pilot trial
Am J Hum Genet. 2024 Dec 5;111(12):2643-2667. doi: 10.1016/j.ajhg.2024.10.020. ABSTRACT Large prospective clinical trials are underway or planned that examine the clinical utility and cost effectiveness of genome-based newborn screening (gNBS). One gNBS platform, BeginNGS, currently screens 53,575 variants for 412 severe childhood genetic diseases with 1,603 efficacious therapies. Retrospective evaluation of BeginNGS in 618,290 […]