The CFTR gene variants in Japanese children with idiopathic pancreatitis

Manami Iso,Kazuhito Satou,Kei Minowa,Tadashi Kaname,Satoshi Nakano,Yumiko Sakurai,Kumiko Yanagi,Mitsuyoshi Suzuki,Toshiaki Shimizu

doi:10.1038/s41439-019-0049-7

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) gene has been reported as one of the pancreatitis susceptibility genes. Although many variants of CFTR have been reported in Caucasian patients, there are few data in Japanese patients. We aimed to survey CFTR variants in Japanese children with idiopathic pancreatitis. Twenty-eight Japanese paediatric patients with idiopathic pancreatitis were enroled, who were not previously diagnosed by genetic analysis of PRSS1 and SPINK1. The entire CFTR gene was sequenced in the patients by combining LA-PCR and next-generation sequencing analysis. To determine a splice-affecting variant, CFTR expression was investigated in the nasal epithelial cells by RT-PCR. One (3.6%) and 15 (53.6%) of 28 patients had pathogenic and functionally affected variants in the CFTR gene, respectively. Two variants, p.Arg352Gln and p.Arg1453Trp, were found more frequently in the patients compared with one in Japanese healthy controls (p = 0.0078 and 0.044, respectively). We confirmed skipping of exon 10 in the nasal epithelial cells in one patient having a splice-affecting variant (c.1210-12 T(5)) in intron 9. Functionally affected variants of the CFTR gene are not so rare in Japanese paediatric patients with idiopathic pancreatitis. Surveying CFTR gene variants in a Japanese sample could help identify pancreatitis risk in these children.

Highlights

There are many risk factors contributing to acute pancreatitis in children
The cystic fibrosis transmembrane conductance regulator (CFTR) gene has been identified as a causative gene for cystic fibrosis (CF)[5] and is reported to be a gene associated with pancreatitis[6,7]
28 Japanese paediatric patients with idiopathic pancreatitis were analysed, who had no pathogenic variants of PRSS1 and serine protease inhibitor Kazal type 1 (SPINK1) by genetic analysis in a previous study[17]

Summary

Introduction

Genetic analysis can be helpful in making the diagnosis of paediatric pancreatitis. The first report of a genetic cause of idiopathic pancreatitis demonstrated mutations in cationic trypsinogen (PRSS1)[1]. Since another causative gene for pancreatitis, serine protease inhibitor Kazal type 1 (SPINK1)[2], and strongly associated genes, such as, chymotrypsinogen (CTRC)[3] and recently carboxypeptiase A1 (CPA1)[4], have been reported. The cystic fibrosis transmembrane conductance regulator (CFTR) gene has been identified as a causative gene for cystic fibrosis (CF)[5] and is reported to be a gene associated with pancreatitis[6,7]. More than 2000 variants of the CFTR gene have been reported[8,9]

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Conclusion