Genetic Analysis of Japanese Children With Acute Recurrent and Chronic Pancreatitis

Saito, Nobutomo; Suzuki, Mitsuyoshi; Sakurai, Yumiko; Nakano, Satoshi; Naritaka, Nakayuki; Minowa, Kei; Sai, Jin Kan; Shimizu, Toshiaki

doi:10.1097/mpg.0000000000001320

Cited by 24 publications

(24 citation statements)

References 37 publications

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“…This is a striking difference between the pediatric and adult cohorts. Several pediatric studies report genetic variants associated with CP, 14,[22][23][24][25][26] whereas adult studies describe environmental risk factors, particularly alcohol and smoking. 12,[27][28][29] Longitudinal and prospective studies that involve pediatric and adult cohorts are needed to determine whether this is related to penetrance of certain mutations in the pediatric group and/or the synergy between genetic and environmental factors.…”

Section: Genetic Associationsmentioning

confidence: 99%

Pancreatitis in Children

2019

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Acute, acute recurrent, and chronic forms of pancreatitis have been increasingly diagnosed in children in the past 2 decades. Risk factors in the pediatric group are broad and appear to be strikingly different compared with the adult cohort. However, the disease burden and impact on quality of life are surprisingly similar in children and adults. This review summarizes the definitions, epidemiology, risk factors, diagnosis, and management of pediatric pancreatitis, identifies features that are unique to the childhood-onset disease, identifies gaps, and proposes recommendations for future opportunities.

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Section: Genetic Associationsmentioning

confidence: 99%

Pancreatitis in Children

2019

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“…Interestingly, mutation p.D100H was also detected in three unaffected members of a French family carrying a complex deletion in the CTRC gene, which was coinherited with p.D100H in one unaffected family member only [ 28 ]. Finally, mutation p.G208A is a relatively common variant in Japanese (∼4% carrier frequency) and Korean (∼8% carrier frequency) cohorts, in which association with idiopathic and alcoholic pancreatitis has been demonstrated [ 22 , 29 – 33 ]. The mutation was also reported in a Slovakian patient with idiopathic chronic pancreatitis [ 34 ].…”

Section: Misfolding Prss1 Variants In Chronic Pancreatitismentioning

confidence: 99%

Genetic risk in chronic pancreatitis: the misfolding-dependent pathway

Sahin–Tóth¹

2017

Current Opinion in Gastroenterology

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Purpose of reviewGenetic risk in chronic pancreatitis is partly due to mutations that cause misfolding of digestive enzymes and elicit endoplasmic reticulum stress. This review examines recent developments in this concept.Recent findingsThe best characterized misfolding variants in the highly expressed digestive proteases cationic trypsinogen (PRSS1) and carboxypeptidase A1 (CPA1) are strong, causative risk factors for chronic pancreatitis and may be associated with autosomal dominant hereditary pancreatitis.SummaryProperties of misfolding digestive enzyme mutants indicate that endoplasmic reticulum stress is a highly relevant pathological mechanism and a potential therapeutic target in chronic pancreatitis.

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“…In total, 28 Japanese paediatric patients with idiopathic pancreatitis were analysed, who had no pathogenic variants of PRSS1 and SPINK1 by genetic analysis in a previous study 17 . In addition, their families and 92 healthy Japanese girls (9–12 years old) were enroled as healthy control subjects.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, there is no information about the genetic risk of CFTR variants in Japanese children with idiopathic pancreatitis. In our previous study, we performed genetic analysis of PRSS1 , SPINK1 , CTRC and CPA1 , finding that 39% (50/128) of paediatric Japanese patients with idiopathic pancreatitis had at least one pathogenic variant of those genes 17 . However, there is no such data for the CFTR gene in this sample.…”

Section: Introductionmentioning

confidence: 99%

The CFTR gene variants in Japanese children with idiopathic pancreatitis

et al. 2019

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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.

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Genetic Analysis of Japanese Children With Acute Recurrent and Chronic Pancreatitis

Abstract: In pediatric patients with idiopathic ARP and CP, genetic analysis is useful for identifying the cause of pancreatitis. Early endoscopic or surgical treatment prevents ARP by extending the interval between episodes of pancreatitis in this population.

Cited by 24 publications

References 37 publications

Pancreatitis in Children

Pancreatitis in Children

Genetic risk in chronic pancreatitis: the misfolding-dependent pathway

The CFTR gene variants in Japanese children with idiopathic pancreatitis

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