CALCB splice region pathogenic variants leading to plasma cell neurotropic enrichment in type 1 autoimmune pancreatitis
| Autor: | Ling Guo, Bin Cai, Qicai Liu, Liqing Lin, Chengfei Zhao, Xinhua Lin, Falin Chen, Chao-yang Wu, Feng Gao, Tianming Zhang, Ze-hao Zhuang, Jin-tong Chen |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cancer Research Pathology medicine.medical_specialty MAP Kinase Signaling System Calcitonin Gene-Related Peptide Plasma Cells Immunology Golgi Apparatus Plasma cell Biology Endoplasmic Reticulum Autoimmune Diseases Cell Line 03 medical and health sciences Cellular and Molecular Neuroscience symbols.namesake 0302 clinical medicine medicine Humans Missense mutation Trypsin splice Phosphorylation Trypsinogen activation Pancreas Autoimmune pancreatitis Inflammation Endoplasmic reticulum HEK 293 cells Cell Biology Golgi apparatus medicine.disease Molecular biology HEK293 Cells 030104 developmental biology medicine.anatomical_structure Pancreatitis 030220 oncology & carcinogenesis Mutation symbols Original Article Female |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Recently, we have demonstrated that PRSS1 mutations cause ectopic trypsinogen activation and thereby result in type 1 autoimmune pancreatitis (AIP). However, the molecules involved in inducing obliterative vasculitis and perineural inflammation in the pancreas are not well-described. The present study applied whole-exome sequencing (WES) to determine the underlying etiology and revealed novel missense splice region variants, CALCB c.88T>C (p.Ser30Pro) and IR [1]-mutants, in 2 of the 3 families and 2 of 26 unrelated patients with type 1 AIP. In vitro, both of the mutants displayed decreased βCGRP, ERK1/2 phosphorylation, and co-localized with endoplasmic reticulum and Golgi apparatus. The novel pathogenic variant identified in this case should contribute to our understanding of the expanding spectrum of AIP. |
| Databáze: | OpenAIRE |
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