Minigenes enhance heterologous expression and prevent aberrant splicing of mouse Spink1.

The digestive enzyme trypsin is an important driver of pancreatitis development and progression. Inhibition of intrapancreatic trypsin activity is an attractive yet so far unsuccessful approach for the treatment and prevention of pancreatitis. Gene therapy using adeno-associated viral vector containing the human serine protease inhibitor Kazal type 1 (SPINK1) gene has shown efficacy against murine pancreatitis in preclinical experiments.

Spontaneous mentalizing in patients with schizophrenia spectrum disorders: a meta-analysis.

Background: Spontaneous mentalizing refers to the capacity to attribute mental states to oneself and others without explicit prompts or conscious deliberation. This process enables individuals to comprehend and anticipate social behaviors in a more intuitive manner. Individuals diagnosed with schizophrenia frequently demonstrate deficits in this domain, which contribute to impaired social functioning.

Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis.

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign.

Novel chymotrypsin C (CTRC) variants from real-world genetic testing of pediatric chronic pancreatitis cases.

Background: Chymotrypsin C (CTRC) protects the pancreas against unwanted intrapancreatic trypsin activity through degradation of trypsinogen. Loss-of-function CTRC variants increase the risk for chronic pancreatitis (CP). The aim of the present study was to characterize novel CTRC variants found during genetic testing of CP cases at a pediatric pancreatitis center.

Risk of chronic pancreatitis in carriers of the c.180C>T (p.Gly60=) CTRC variant: case-control studies and meta-analysis.

Chymotrypsin C (CTRC) is a digestive serine protease produced by the pancreas that regulates intrapancreatic trypsin activity and provides a defensive mechanism against chronic pancreatitis (CP). CTRC exerts its protective effect by promoting degradation of trypsinogen, the precursor to trypsin. Loss-of-function missense and microdeletion variants of CTRC are found in around 4% of CP cases and increase disease risk by approximately 3-7-fold.

Bicarbonate defective CFTR variants increase risk for chronic pancreatitis: A meta-analysis.

Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) plays a central role in pancreatic ductal fluid secretion by mediating Cl- and HCO3- ion transport across the apical membrane. Severe CFTR mutations that diminish chloride conductance cause cystic fibrosis (CF) if both alleles are affected, whereas heterozygous carrier status increases risk for chronic pancreatitis (CP). It has been proposed that a subset of CFTR variants characterized by a selective bicarbonate conductance defect (CFTRBD) may be associated with CP but not CF.

Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis.

The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally.

Common calcium-sensing receptor (CASR) gene variants do not modify risk for chronic pancreatitis in a Hungarian cohort.

The calcium-sensing receptor (CASR) is expressed in the pancreas where it might regulate calcium concentrations in pancreatic secretions. Two independent studies reported conflicting results claiming that commonly occurring missense variants of the CASR gene are risk factors for chronic pancreatitis (CP). Here, we attempted to replicate the association between CASR variants and CP.