Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency
Nat Genet. 2026 Sep 24. doi: 10.1038/s41588-026-02745-1. Online ahead of print. ABSTRACT Medulloblastoma is a biologically heterogeneous childhood cerebellar tumor harboring frequent chromatin-modifying gene alterations. How these alterations promote transcriptional programs governing malignancy remains poorly defined. To address this knowledge gap, we evaluated chromatin states across medulloblastoma subgroups by multi-modal integration of histone modifications with […]
Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of GOT2 Deficiency: A Progressive Neurodevelopmental Disorder with Epilepsy and Abnormal Movements
Genet Med. 2025 Sep 22:101587. doi: 10.1016/j.gim.2025.101587. Online ahead of print. ABSTRACT PURPOSE: Glutamic-oxaloacetic transaminase (GOT), also known as aspartate aminotransferase, catalyzes the reversible transamination of oxaloacetate and glutamate to aspartate and α-ketoglutarate. Two isoforms, cytosolic (GOT1) and mitochondrial (GOT2), are integral to the malate-aspartate shuttle (MAS), a key regulator of intracellular redox homeostasis. Recently, […]
Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing
Proc Natl Acad Sci U S A. 2026 Sep 22;123(38):e2531269123. doi: 10.1073/pnas.2531269123. Epub 2026 Sep 14. ABSTRACT Medulloblastomas are considered immunologically cold and refractory to immunotherapy. One factor contributing to their low immunogenicity is impaired antigen presentation, which allows tumor cells to evade cytotoxic T cells. Using a syngeneic mouse model of medulloblastoma, we demonstrate […]
PIGC-related encephalopathy: Lessons learned from 18 new probands
Eur J Hum Genet. 2025 Sep 17. doi: 10.1038/s41431-025-01923-9. Online ahead of print. ABSTRACT PIGC encodes a protein essential for the biosynthesis of glycophosphatidylinositol-anchored proteins (GPI-APs). So far, three families with biallelic PIGC variants have been reported to exhibit developmental delay/intellectual disability and seizures. Our aim was to further elucidate the clinical and biomolecular characteristics […]
Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease
EMBO Mol Med. 2026 Sep 8. doi: 10.1038/s44321-026-00497-3. Online ahead of print. ABSTRACT Genome sequencing is the first-line diagnostic method for primary mitochondrial diseases (PMDs), yet its effectiveness is limited by variants of uncertain significance or unresolved genetic findings. We systematically evaluated the clinical performance of fibroblast-based functional testing, comprised of respiratory chain enzyme assays, […]
A clinical and genotype-phenotype analysis of MACF1 variants
Am J Hum Genet. 2025 Sep 3:S0002-9297(25)00320-9. doi: 10.1016/j.ajhg.2025.08.010. Online ahead of print. ABSTRACT Microtubule-actin cross-linking factor 1 (MACF1) is a large protein of the spectraplakin family, which is essential for brain development. MACF1 interacts with microtubules through the growth arrest-specific 2 (Gas2)-related (GAR) domain. Heterozygous MACF1 missense variants affecting the zinc-binding residues in this […]
AAV-mediated CBLN1 replacement rescues hereditary ataxia caused by biallelic CBLN1 variants
Mol Ther. 2026 Sep 2:S1525-0016(26)00772-0. doi: 10.1016/j.ymthe.2026.09.003. Online ahead of print. ABSTRACT Cbln1 is a secreted synaptic organizer required for parallel fiber-Purkinje cell (PF-PC) synapse integrity, climbing fiber (CF) refinement, and cerebellar motor learning, but has not previously been implicated in human disease. We identified biallelic CBLN1 missense variants (A63P and Y112C) in two unrelated […]
The Fetal Fentanyl Syndrome: Additional evidence in support of a new human teratogen
Genet Med. 2026 Aug 25:102698. doi: 10.1016/j.gim.2026.102698. Online ahead of print. ABSTRACT PURPOSE: Prenatal opioid exposure has inconsistently been associated with congenital anomalies. In 2023, fentanyl was proposed as a human teratogen in ten infants with documented exposure and a consistent pattern of abnormalities. Disrupted cholesterol biosynthesis was proposed as the pathogenetic mechanism. METHODS: We […]
Honeybadger, a micropeptide encoded by an alternative PVT1 transcript, is a critical negative regulator of RAS-MAPK signaling in MYC-driven tumors
Genes Dev. 2026 Aug 19. doi: 10.1101/gad.353356.125. Online ahead of print. ABSTRACT Genomic rearrangements can drive cancer through mechanisms that extend beyond classical oncogenic fusions such as BCR-ABL A substantial fraction of these events involve long noncoding RNAs (lncRNAs), yet their functional impact on tumorigenesis has remained largely opaque. The lncRNA plasmacytoma variant translocation 1 […]
Firefox, a protein encoded by circular PVT1, is essential for MYC-driven oncogenesis
Genes Dev. 2026 Aug 19. doi: 10.1101/gad.353355.125. Online ahead of print. ABSTRACT MYC-driven (MYC+) cancers are highly aggressive and often fatal. MYC dysregulation is a key event in these cancers, yet MYC overexpression alone is often insufficient to initiate or sustain tumorigenesis. Plasmocytoma variant translocation 1 (PVT1), a long noncoding RNA (lncRNA) adjacent to MYC […]