The value and significance of gene sequencing in the diagnosis of pediatric pancreatitis / 中国小儿急救医学

Genetics has become one of the most important factors in the etiology of pediatric pancreatitis with advances in technology and clinical studies.Variations in these genes may increase the risk of acute recurrent and chronic pancreatitis in children, accelerate progression to endocrine and exocrine pancreatic insufficiency, and increase the risk of pancreatic cancer in adulthood.This review summarized the clinical research on the relationship between gene variations and pancreatitis, elaborated on the mechanisms, risks, and clinical phenotypes of pancreatitis caused by different gene variations, and analyzed the significance of related gene sequencing in children with pancreatitis.It aims to help pediatricians know the indications of gene sequencing in pediatric pancreatitis and do much better in relevant diagnosis, prognosis evaluation, and genetic counseling.

Report of a pedigree of mitochondrial diabetes mellitus complicated with chronic hereditary pancreatitis / 中华内分泌代谢杂志

This study reported a family of mitochondrial diabetes mellitus complicated with chronic hereditary pancreatitis. A 18-year-old woman presented with self-reported hyperglycemia and chronic epigastric pain was admitted to our hospital. Clinical data and family history were collected. Mitochondrial gene sequencing and whole exon gene sequencing showed that the proband carried mutation of mt.3243A>G and heterozygous mutation of SPINK1 c. 194+ 2T>C, which was considered as mitochondrial diabetes mellitus with chronic pancreatitis.

The Role of Genetic Mutation in the Pathogenesis of Pancreatitis / 대한췌담도학회지

10–30% of patients with pancreatitis can be categorized as idiopathic pancreatitis, and some of them may be due to genetic alterations. Since hereditary pancreatitis develops from pediatric patients with symptoms related to pancreatitis, which usually progresses to chronic pancreatitis around 30 years of age, special attention should be paid to the development of pancreatic cancer in such patients. Up to now, there have been more than 30 genetic alterations associated with pancreatitis. Alterations in protease serine 1 (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR) and chymotrypsin C (CTRC) are common, which show diversity according to race and region. It is important to understand the characteristics of Korean patients with idiopathic pancreatitis through genetic studies. The purpose of this article is to review the role of genetic variations in the pathophysiology of idiopathic pancreatitis and to survey the results of Korean studies of idiopathic pancreatitis.

Multisite Heterozygous Mutations of PRSS1 Gene and Clinical Characterization of Patients With Hereditary Pancreatitis in The Chinese / 生物化学与生物物理进展

In four patients with chronic pancreatitis from two hereditary pancreatitis (HP) families and 63 normal controls, five exons of cationic trypsinogen gene (PRSS1) were amplified by PCR and it's products were analyzed by sequencing, related clinical data were also collected. All the four patients were found mutations in the PRSS1 gene but their clinical feature is absolutely different. Six patients with diabetes mellitus were found in pedigree No. 1, it's members show pancreatitis symptom later, at about 29, the tumor markers (CA19-9, CA72-4) is obviously higher than the patients in pedigree No. 2, two patients with chronic pancreatitis in pedigree No. 2, show symptom earlier without diabetes mellitus, their clinical characterization are different too. The number of CD4+T cell/CD8+T is very low in Ⅲ 8, but Ⅲ 7 is normal, and the level of anti-HBs of Ⅲ 8 is variable in the course of pancreatitis, but the phenomenon was not found in Ⅲ 7. In their PRSS1 gene two guanosine (G) to adenosine (A) mutations were found in PRSS1 exon 3 of pedigree No. 1, one was detected at 336 basyl, the other mutation occurs at 361 basyl. The results of the mutations were Lys →Lys and Ala →Thr. While thymine (T) to adenosine (A) and (guanosine) G→(adenosine) A mutation in PRSS1 exon 3 was detected in the other patient of pedigree No. 2 (Ⅲ 8). One was 361 basyl, the other at 415 basyl. While c.415 T→A was not found in the proband of pedigree No. 2 PRSS1 gene (Ⅲ 7). All of the mutations were heterozygous mutation, that is to say all of the trypsinogen were wild type and mutant type concomitance, the normal and abnormal pathway of active trypsinogen exist partially. At the same time, the mutations of SPINK1 were not observed. Compared with the documents and registration of NCBI, it can be concluded that PRSS1 gene had many kinds of mutations in hereditary pancreatitis, the heterozygous mutations (c.336 G→A, c.415 T→A) were the novel mutations and related with clinical phenotype. What's more, it's the first time that the multisite heterozygous mutations of PRSS1 gene were reported. The presence of the mutations in four patients with chronic pancreatitis, it's absence in their relatives and the strong evolutionary conservation of the mutation, all indicate that the trypsinogen mutation is associated with hereditary pancreatitis and for the first time raises the question whether a gain or a loss of trypsin function participates in the onset of Chinese pancreatitis.

A case of hereditary pancreatitis with a N29I mutation in the cationic trypsinogen gene / 소아과

Hereditary pancreatitis is an autosomal dominant disease characterized by recurrent episodes of pancreatitis, often beginning in childhood, with a positive family history involving at least two other affected family members with no known other precipitating factors. Most forms of hereditary pancreatitis are caused by one of two common mutations, i.e., R122H in exon 3 and N29I in exon 2 of the cationic trypsinogen (CT) (PRSS1) gene, located on chromosome 7. The authors describe the case of a 15-year-old boy who had suffered from recurrent attacks of pancreatitis since age three. His mother and grandmother had chronic pancreatitis and diabetes mellitus. Mutation analysis was performed on the family due to the suspicion of hereditary pancreatitis. The CT gene was analyzed in DNA samples extracted from the peripheral blood of three family members, the mother, the proband, and the proband's sister. Two members of the family, the mother and the proband, were found to have a N29I mutation in the CT gene. The authors document the first family with hereditary pancreatitis associated with the N29I mutation in Korea.

Hereditary Pancreatitis: Report of a Kindred

Hereditary pancreatitis (HP) appears as an autosomal dominant trait. If the patient has (1) more than 2 affected relatives in different generations and (2) no known etiological factors such as alcohol or gallstones, or has R122H or N29I mutation in the cationic trypsinogen (CT) gene, the diagnosis of HP can be applied. Risk of pancreatic cancer is estimated to be 53-fold higher than in a general population after the age of 50 years. We report a kindredof HP, involving three of its family together; two siblings (14 years old, 13 years old) and cousin (26 years old). The patient had complicating chronic pancreatitis and pancreatic stone, and was treated with amodified Puestow-Gillesby procedure. Her sisters showed chronic pancreatitis. Her cousin underwent a drainage procedure of the pancreatic duct for chronic pancreatitis during the high school period. All the three members showed the R122H mutation of the CT gene.

Hereditary Pancreatitis: Report of a Kindred

Hereditary pancreatitis (HP) appears as an autosomal dominant trait. If the patient has (1) more than 2 affected relatives in different generations and (2) no known etiological factors such as alcohol or gallstones, or has R122H or N29I mutation in the cationic trypsinogen (CT) gene, the diagnosis of HP can be applied. Risk of pancreatic cancer is estimated to be 53-fold higher than in a general population after the age of 50 years. We report a kindredof HP, involving three of its family together; two siblings (14 years old, 13 years old) and cousin (26 years old). The patient had complicating chronic pancreatitis and pancreatic stone, and was treated with amodified Puestow-Gillesby procedure. Her sisters showed chronic pancreatitis. Her cousin underwent a drainage procedure of the pancreatic duct for chronic pancreatitis during the high school period. All the three members showed the R122H mutation of the CT gene.

Hereditary Pancreatitis / 대한소화기학회지

The first family of hereditary pancreatitis was described in 1952. The mode of inheritance is autosomal dominant trait with an 80% of penetrance rate. Although hereditary pancreatitis is rare, this disorder has provided valuable insights in understanding the pathophysiology of pancreatitis and pancreatic cancer. The causative gene of hereditary pancreatitis was identified in 1996 through mutational analysis of genes within chromosome 7q35. Most forms of hereditary pancreatitis are caused by one of two common mutations, R122H in the third exon or N29I in the second exon of the cationic trypsinogen gene (protease serine 1, PRSS1). R122H mutation is the most common PRSS1 mutation. Additional mutations of the cationic trypsinogen gene have been described. In Korea, first family of hereditary pancreatitis with cationic trypsinogen gene mutation revealed an arginine to histidine amino acid substitution at the residue 122. Patients with hereditary pancreatitis present with symptoms at an early age and have significant risk for the development of chronic pancreatitis and pancreatic cancer. The risk of pancreatic cancer is estimated to be 53-fold higher after the age of 50 years than the general population. The risk of pancreatic cancer is not related to the type of mutation. Since hereditary pancreatitis is a strong risk factor for pancreatic cancer, it is important to establish a diagnostic criteria for diagnosis and surveillance. However, there are potential benefits, risks and limitations in genetic testing for hereditary pancreatitis. It is difficult to provide the proper treatment, but recent developments in therapeutic approaches may be helpful in caring hereditary pancreatitis. This article includes the current status, pathogenesis, clinical features, and management of hereditary pancreatitis including the aspects of pancreatic cancer.

Hereditary Pancreatitis / 대한소화기학회지

Hereditary pancreatitis (HP) is an autosomal dominant inherited disease characterized by recurrent episodes of pancreatitis often beginning in childhood, a family history of at least 2 other affected members, and the absence of known etiologic factors. The discovery of mutations in cationic trypsinogen gene (PRSS1) in HP not only provided insights into the molecular mechanisms of pancreatitis, but also opened a new era in the field of chronic pancreatitis. The detection of mutations in serine protease inhibitor, Kazal type 1 (SPINK1) and CFTR in patients with hereditary or idiopathic chronic pancreatitis has placed the emphasis on the importance of genetic mutations in pancreatitis. Because the estimated cumulative risk of pancreatic cancer developement in hereditary pancreatitis is nearly 40%, screening tests are important in selected cases. There are no specific medical therapies recommended in patients with HP. Registration of patients with Nationwise Registries is essential if management strategies are to be improved and genetic research to be continued.