Genetic variation in the metabotropic glutamate receptor 3 (GRM3, mGluR3) has been associated with schizophrenia, but the mechanism by which it confers risk is unknown. Previously, we reported the existence of a splice variant, GRM3Delta4, which has an exon 4 deletion and encodes a truncated form of the receptor that is expressed in brain. The aim of the present study was to determine whether expression of this splice variant is altered in individuals with schizophrenia and is affected by a risk genotype. We measured GRM3 and GRM3Delta4 transcripts in human dorsolateral prefrontal cortex (DLPFC) and hippocampus of the CBDB/NIMH collection ( approximately 70 controls, approximately 30 schizophrenia patients) and in the DLPFC of the Stanley Array Collection. Expression data of GRM3 mRNA in the DLPFC were inconsistent: GRM3 was increased in schizophrenia patients in the CBDB/NIMH collection, but not in the Stanley Array Collection. GRM3 expression did not change in the frontal cortex of rats treated chronically with haloperidol or clozapine. An exon 3 SNP previously associated with schizophrenia (rs2228595) predicted increased expression of the GRM3Delta4 splice variant. Our results suggest that rs2228595, or a neighboring SNP in linkage disequilibrium with it, may contribute to risk for schizophrenia by modulating GRM3 splicing.
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http://dx.doi.org/10.1038/sj.npp.1301669 | DOI Listing |
Purpose Of Review: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating heritable channelopathy that can lead to sudden cardiac death in children and young adults. This review aims to explore genetics, the cardiac and extracardiac manifestations of mutations associated with CPVT, and the challenges involved with managing phenotypically variable variants.
Recent Findings: The understanding of the genetics and mechanisms of CPVT continues to grow with recent discoveries including alternative splicing of cardiac TRDN and calmodulin gene variants.
Reprod Biol Endocrinol
January 2025
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Breast cancer (BrCa) is a complex and heterogeneous disease with diverse molecular subtypes, leading to varied clinical outcomes and posing significant treatment challenges. The increasing global burden of BrCa, particularly in low- and middle-income countries, underscores the urgent need for more effective therapeutic strategies. The androgen receptor (AR), expressed in a substantial proportion of breast cancer cases, has emerged as a potential biomarker and therapeutic target.
View Article and Find Full Text PDFJ Transl Med
January 2025
Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, China.
Background: Death-Associated Protein Kinase 1 (DAPK1) family members are calcium/calmodulin-regulated serine/threonine kinases implicated in cell death, normal development, and human diseases. However, the regulation of DAPK1 expression in cancer remains unclear.
Methods: We examined the expression and functional impact of a DAPK1 splice variant, DAPK1-215, in multiple cancer cell lines.
Genomics Proteomics Bioinformatics
January 2025
Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA.
Tumor-specific antigens, also known as neoantigens, have potential utility in anti-cancer immunotherapy, including immune checkpoint blockade (ICB), neoantigen-specific T cell receptor-engineered T (TCR-T), chimeric antigen receptor T (CAR-T), and therapeutic cancer vaccines (TCVs). After recognizing presented neoantigens, the immune system becomes activated and triggers the death of tumor cells. Neoantigens may be derived from multiple origins, including somatic mutations (single nucleotide variants, insertion/deletions, and gene fusions), circular RNAs, alternative splicing, RNA editing, and polymorphic microbiome.
View Article and Find Full Text PDFMol Genet Genomic Med
January 2025
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder. Although individuals with variants in the SMC1A gene are less commonly seen in CdLS, they exhibit a high incidence of epilepsy and atypical phenotypic variability.
Methods: The clinical data of a patient with non-classic CdLS and epilepsy caused by an SMC1A variant were summarized.
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