CALCB splice region pathogenic variants leading to plasma cell neurotropic enrichment in type 1 autoimmune pancreatitis.
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.
Department of Laboratory Medicine, The 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Qi-Cai
QC
Liu
Fujian Provincial Center for Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, China.
Falin
F
Chen
Department of Orthopedics, The 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Chao-Yang
CY
Wu
Department of Pathology, The 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Feng
F
Gao
Department of Gastroenterology, The 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Ze-Hao
ZH
Zhuang
Department of Gastroenterology, The 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Jin-Tong
JT
Chen
Department of Neurology, the 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Bin
B
Cai
Department of Pathology, The 1st Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Tianming
T
Zhang
Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
Ling
L
Guo
Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
Li-Qing
LQ
Lin
Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
Cheng-Fei
CF
Zhao
Department of Pharmaceutical Analysis, Fujian Medical University, Fuzhou, China.
Xin-Hua
XH
Lin
D001327:Autoimmune Diseases / Q000235:genetics* / Q000473:pathology*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000235:genetics; D005260:Female; D006056:Golgi Apparatus / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics* / Q000473:pathology*; D010766:Phosphorylation / Q000235:genetics; D010950:Plasma Cells / Q000473:pathology*; D014357:Trypsin / Q000235:genetics
D014357:Trypsin; D015740:Calcitonin Gene-Related Peptide