遺伝性膵炎
- 同
- HP
WordNet
- inflammation of the pancreas; usually marked by abdominal pain
PrepTutorEJDIC
- 世襲の,親譲りの / 遺伝的な,遺伝性の
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/05/18 22:03:52」(JST)
[Wiki en表示]
Hereditary pancreatitis |
Classification and external resources |
OMIM |
167800 |
DiseasesDB |
30026 |
Hereditary pancreatitis (HP) is an inflammation of the pancreas, attributed to genetic causes. It was first described in 1952 by Comfort and Steinberg[1] but it was not until 1996 that Whitcomb et al[2] isolated the first responsible mutation in the cationic trypsinogen gene (PRSS1) on the long arm of chromosome seven (7q35).
The term "hereditary pancreatitis" is used when a genetic defect is identified, and "familial pancreatitis" used when it is not.[3]
Contents
- 1 Presentation
- 2 Diagnosis
- 3 Genetics
- 4 References
Presentation
HP is characterised by attacks of epigastric pain, which are often associated with nausea and vomiting. Symptoms may start shortly after birth but onset varies greatly, with some individuals not exhibiting symptoms until adulthood. There is usually progression to chronic pancreatitis with endocrine and exocrine failure and a greatly increased risk of pancreatic cancer. Lifetime risk of cancer has been variously calculated as 35–54%[4][5][6] to the age of 75 years and screening for early pancreatic cancer is being offered to HP sufferers on a research basis.[7] Some patients may choose to have their pancreas surgically removed to prevent cancer developing in the future.[8]
The natural history of HP follows a similar pattern to alcohol-associated chronic pancreatitis, but there are important differences, for example, HP has an earlier age of onset of pancreatitis although malabsorption and diabetes mellitus occur at a later stage in the disease.[5]
Diagnosis
Families are defined as having HP,[5] if the phenotype is consistent with highly penetrant autosomal dominant inheritance. In simple terms, this would require two or more first degree relatives (or three or more second degree relatives) to have unexplained recurrent-acute or chronic pancreatitis in two or more generations. It is an autosomal dominant disease with penetrance that is generally accepted to be ≈80%.[1][9]
Genetics
The vast majority of the cases of HP are caused by substitutions, at base 365 (c.365G>A) and base 86 of the cDNA (c.86A>T) on the PRSS1 gene. They were discovered in the late 1990s by conventional linkage analysis[2][10] and are now known as p.R122H and p.N29I respectively, according to the amino acid substitution and position in the protein sequence.
These mutations are rarely identified in general screens of patients with idiopathic disease[11][12][13][14] and the phenotype of p.R122H and p.N29I is now well characterised[4][5][6] with the p.A16V mutation recently characterised for the first time.[15] There are many other rare mutations or polymorphisms of PRSS1 which remain less well understood[16][17] and not all HP families have had the responsible genetic mutation identified.
The mechanism by which these genetic mutations cause pancreatitis is incompletely understood but is likely to be the result of increased autoactivation[18] or reduced deactivation[19] of trypsinogen (or a combination of the two), although a novel mechanism has recently been identified in a p.R116C kindred.[20]
References
- ^ a b Comfort MW, Steinberg AG (May 1952). "Pedigree of a family with hereditary chronic relapsing pancreatitis". Gastroenterology 21 (1): 54–63. PMID 14926813.
- ^ a b Whitcomb DC, Gorry MC, Preston RA et al. (October 1996). "Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene". Nat. Genet. 14 (2): 141–5. doi:10.1038/ng1096-141. PMID 8841182.
- ^ Cheifetz, Adam S.; Brown, Alphonso; Curry, Michael; Alan C. Moss (2011-03-10). Oxford American Handbook of Gastroenterology and Hepatology. Oxford University Press US. pp. 223–. ISBN 978-0-19-538318-8. Retrieved 9 August 2011.
- ^ a b Lowenfels AB, Maisonneuve P, DiMagno EP et al. (March 1997). "Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group". J. Natl. Cancer Inst. 89 (6): 442–6. doi:10.1093/jnci/89.6.442. PMID 9091646.
- ^ a b c d Howes N, Lerch MM, Greenhalf W et al. (March 2004). "Clinical and genetic characteristics of hereditary pancreatitis in Europe". Clin. Gastroenterol. Hepatol. 2 (3): 252–61. doi:10.1016/S1542-3565(04)00013-8. PMID 15017610.
- ^ a b Rebours V, Boutron-Ruault MC, Schnee M et al. (January 2008). "Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series". Am. J. Gastroenterol. 103 (1): 111–9. doi:10.1111/j.1572-0241.2007.01597.x. PMID 18184119.
- ^ Greenhalf W, Grocock C, Harcus M, Neoptolemos J (2009). "Screening of high-risk families for pancreatic cancer". Pancreatology 9 (3): 215–22. doi:10.1159/000210262. PMID 19349734.
- ^ Wolfgang, CL; Herman, JM; Laheru, DA; Klein, AP; Erdek, MA; Fishman, EK; Hruban, RH (Sep 2013). "Recent progress in pancreatic cancer.". CA: a cancer journal for clinicians 63 (5): 322–323. doi:10.3322/caac.21190. PMC 3769458. PMID 23856911.
- ^ Whitcomb DC (September 1999). "Hereditary pancreatitis: new insights into acute and chronic pancreatitis". Gut 45 (3): 317–22. doi:10.1136/gut.45.3.317. PMC 1727629. PMID 10446089.
- ^ Gorry MC, Gabbaizedeh D, Furey W et al. (October 1997). "Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis". Gastroenterology 113 (4): 1063–8. doi:10.1053/gast.1997.v113.pm9322498. PMID 9322498.
- ^ Chen JM, Piepoli Bis A, Le Bodic L et al. (March 2001). "Mutational screening of the cationic trypsinogen gene in a large cohort of subjects with idiopathic chronic pancreatitis". Clin. Genet. 59 (3): 189–93. doi:10.1034/j.1399-0004.2001.590308.x. PMID 11260229.
- ^ Lee KH, Yoon WJ, Ryu JK, Kim YT, Yoon YB, Kim CY (August 2004). "[Mutations of SPINK1 and PRSS1 gene in Korean patients with chronic pancreatitis]". Korean J Gastroenterol (in Korean) 44 (2): 93–8. PMID 15329520.
- ^ O'Reilly DA, Yang BM, Creighton JE, Demaine AG, Kingsnorth AN (2001). "Mutations of the cationic trypsinogen gene in hereditary and non-hereditary pancreatitis". Digestion 64 (1): 54–60. doi:10.1159/000048839. PMID 11549837.
- ^ Witt H, Luck W, Becker M (July 1999). "A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis". Gastroenterology 117 (1): 7–10. doi:10.1016/s0016-5085(99)70543-3. PMID 10381903.
- ^ Grocock CJ, Rebours V, Delhaye MN et al. (March 2010). "The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families". Gut 59 (3): 357–63. doi:10.1136/gut.2009.186817. PMID 19951905.
- ^ Teich N, Rosendahl J, Tóth M, Mössner J, Sahin-Tóth M (August 2006). "Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis". Hum. Mutat. 27 (8): 721–30. doi:10.1002/humu.20343. PMC 2793115. PMID 16791840.
- ^ Szmola R, Sahin-Tóth M (May 2010). "Uncertainties in the classification of human cationic trypsinogen (PRSS1) variants as hereditary pancreatitis-associated mutations". J. Med. Genet. 47 (5): 348–50. doi:10.1136/jmg.2009.072751. PMC 2930840. PMID 20452997.
- ^ Sahin-Tóth M (June 2006). "Biochemical models of hereditary pancreatitis". Endocrinol. Metab. Clin. North Am. 35 (2): 303–12, ix. doi:10.1016/j.ecl.2006.02.002. PMC 1602208. PMID 16632094.
- ^ Felderbauer P, Schnekenburger J, Lebert R et al. (August 2008). "A novel A121T mutation in human cationic trypsinogen associated with hereditary pancreatitis: functional data indicating a loss-of-function mutation influencing the R122 trypsin cleavage site". J. Med. Genet. 45 (8): 507–12. doi:10.1136/jmg.2007.056481. PMID 18511571.
- ^ Kereszturi E, Szmola R, Kukor Z et al. (April 2009). "Hereditary pancreatitis caused by mutation-induced misfolding of human cationic trypsinogen: a novel disease mechanism". Hum. Mutat. 30 (4): 575–82. doi:10.1002/humu.20853. PMC 2663013. PMID 19191323.
Congenital malformations and deformations of digestive system (Q35–Q45, 749–751)
|
|
Upper GI tract |
Tongue, mouth and pharynx |
- Cleft lip and palate
- Van der Woude syndrome
- tongue
- Ankyloglossia
- Macroglossia
- Hypoglossia
|
|
Esophagus |
- EA/TEF
- Esophageal atresia: types A, B, C, and D
- Tracheoesophageal fistula: types B, C, D and E
- esophageal rings
- Esophageal web (upper)
- Schatzki ring (lower)
|
|
Stomach |
- Pyloric stenosis
- Hiatus hernia
|
|
|
Lower GI tract |
Intestines |
- Intestinal atresia
- Meckel's diverticulum
- Hirschsprung's disease
- Intestinal malrotation
- Dolichocolon
- Enteric duplication cyst
|
|
Rectum/anal canal |
- Imperforate anus
- Vestibular fistula
- Persistent cloaca
- Rectal atresia
|
|
|
Accessory |
Pancreas |
- Annular pancreas
- Accessory pancreas
- Johanson–Blizzard syndrome
- Pancreas divisum
|
|
Bile duct |
- Choledochal cysts
- Biliary atresia
|
|
Liver |
- Alagille syndrome
- Polycystic liver disease
|
|
|
Index of the mouth
|
|
Description |
|
|
Disease |
- Congenital
- face and neck
- cleft
- digestive system
- Neoplasms and cancer
- Other
- Symptoms and signs
|
|
Treatment |
|
Index of digestion
|
|
Description |
- Anatomy
- Physiology
- Development
|
|
Disease |
- Congenital
- Neoplasms and cancer
- Inflammatory bowel disease
- Gluten sensitivity
- Other
- Symptoms and signs
- Blood tests
|
|
Treatment |
- Procedures
- Drugs
- anabolic steroids
- antacids
- diarrhoea and infection
- bile and liver
- functional gastrointestinal disorders
- laxatives
- peptic ulcer and reflux
- nausea and vomiting
- other
- Surgery
|
|
|
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- An overview of hereditary pancreatitis.
- Rebours V, Levy P, Ruszniewski P.SourcePole des Maladies de l'Appareil Digestif, Service de Gastroenterologie - Pancreatologie, Hopital Beaujon, AP-HP, Universite Denis Diderot-Paris VII, Clichy, France.
- Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.Dig Liver Dis.2011 Sep 8. [Epub ahead of print]
- Hereditary pancreatitis is a rare cause of chronic pancreatitis. The prevalence was evaluated to 0.3/100000 in Western Countries. Genetic disorders are due to mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal
- PMID 21907651
- Familial pancreatic cancer and hereditary syndromes: screening strategy for high-risk individuals.
- Matsubayashi H.SourceDivision of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan, h.matsubayashi@scchr.jp.
- Journal of gastroenterology.J Gastroenterol.2011 Aug 17. [Epub ahead of print]
- Globally, and almost evenly across nations, a familial disposition can be found in 4-10% of patients with pancreatic cancer (PC). A family history of PC is a risk for this disease and the risk level changes in correlation with the number of affected relatives. Several hereditary syndromes with poten
- PMID 21847571
Japanese Journal
- 正宗 淳,中野 絵里子,粂 潔,新堀 哲也,青木 洋子,下瀬川 徹
- 膵臓 29(1), 51-58, 2014
- 1996年,遺伝性膵炎の原因としてカチオニックトリプシノーゲン(PRSS1)遺伝子変異が同定されて以降,種々の膵炎関連遺伝子異常が報告されてきた.これまでは膵分泌性トリプシンインヒビター(SPINK1)遺伝子など,トリプシンの活性化・不活性化に関わる遺伝子異常が中心であった.最近,遺伝子異常の結果,膵腺房細胞内に小胞体ストレスを起こすことが,新たな膵炎発症機序として注目されている.家族歴の濃厚な遺 …
- NAID 130004496051
- Genetics of Pancreatitis: The 2014 Update
- Masamune Atsushi
- The Tohoku Journal of Experimental Medicine 232(2), 69-77, 2014
- … Chronic pancreatitis is a progressive inflammatory disease in which pancreatic secretory parenchyma is destroyed and replaced by fibrous tissue, eventually leading to malnutrition and diabetes. … Since the identification of mutations in the cationic trypsinogen (PRSS1) gene as a cause of hereditary pancreatitis in 1996, we have seen great progress in our understanding of the genetics of pancreatitis. …
- NAID 130004460109
- 加藤 浩之,太田 明雄,佐田 幸由,福田 尚志,方波見 卓行,田中 逸
- 糖尿病 54(11), 856-859, 2011-11-30
- NAID 10030976327
Related Links
- Hereditary Pancreatitis (HP) is an inflammation of the pancreas, attributed to genetic causes. It was first described in 1952 by Comfort and Steinberg [1] but it was not until 1996 that Whitcomb et al [2] isolated the first responsible ...
- Hereditary Pancreatitis (HP) is an inflammation of the pancreas, attributed to genetic causes. It was first described in 1952 by Comfort and Steinberg [1] but it was not until 1996 that Whitcomb et al [2] isolated the first responsible ...
Related Pictures
★リンクテーブル★
[★]
[★]
- 英
- hereditary pancreatitis
[★]
- 関
- heredity、heritable、inherit、inheritable、inheritable character、inheritance、inherited