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, […]
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 […]
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 […]
Individualized antisense oligonucleotides for SCN2A-related developmental epileptic encephalopathy
Nat Med. 2026 Jul 21. doi: 10.1038/s41591-026-04527-y. Online ahead of print. ABSTRACT SCN2A variants are among the most common genetic causes of developmental and epileptic encephalopathies (DEEs), which can present with uncontrolled seizures at birth and account for 1-2% of all epileptic encephalopathies. A substantial fraction of causal variants are gain-of-function or mixed-function variants associated […]
Follow-up and outcome of patients with primary BH4 deficiencies
Front Neurol. 2026 Jul 16;17:1793300. doi: 10.3389/fneur.2026.1793300. eCollection 2026. ABSTRACT BH4 deficiencies may occur with or without hyperphenylalaninemia (HPA). If identified early through neonatal screening for PKU, the clinical follow-up aims to prevent the onset of typical disease symptoms. In contrast, for the conditions not associated with HPA, diagnosis usually occurs once symptoms manifest, and […]
Novel Therapeutic Treatments in Perinatal Genetics Bridging Prenatal and Postnatal Care of Genetic Conditions
Clin Ther. 2026 Jun 9:S0149-2918(26)00188-8. doi: 10.1016/j.clinthera.2026.05.025. Online ahead of print. NO ABSTRACT PMID:42264972 | DOI:10.1016/j.clinthera.2026.05.025