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 […]
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 […]