ABCMdb

PMID: 22749696

Chen JM, Ferec C
Genetics and pathogenesis of chronic pancreatitis: the 2012 update.
Clin Res Hepatol Gastroenterol. 2012 Aug;36(4):334-40. doi: 10.1016/j.clinre.2012.05.003. Epub 2012 Jun 30., [PubMed]

Sentences

No. Mutations Sentence Comment

67 ABCC7 p.Gln1352His Missense mutation [first description] Occurrence Known co-inherited variant(s) Experimentally demonstrated functional consequence Pathogenic relevance Previously analyzed L12F [43] Common polymorphism - No significant loss of PSTI expression [43] No L14R [43] Rare - 20% of PSTI expression [43] Yes L14P [5] Rare - No PSTI expression [43] Yes N34S [73] Common polymorphism See text No significant loss of PSTI expression [42,44,48] See text G48E [42] Rare - No PSTI expression [42] Yes D50E [74] Rare - No PSTI expression [42,44] Yes Y54H [75] Rare - <5% of normal PSTI expression [42,44] Yes P55S [73] Common polymorphism - No significant loss of PSTI expression [42,44] No R65Q [76] Rare - 40% of normal PSTI expression[42,44] Yes R67C [77] Rare - Barely detectable PSTI expression [42,44] Yes Newly analyzed S10N [45] Rare - No significant loss of PSTI expression [45] No N37S [78] Rare SPINK1 N34S and CFTR Q1352H No significant loss of PSTI expression [45] No N64D [45] Rare - No PSTI expression [45] Yes K66N [78] Rare - No PSTI expression [45] Yes R67H [45] Rare - No PSTI expression [45] Yes Q68R [78] Rare PRSS1 N29I Significantly increased PSTI expression [45] See text T69I [79] Rare - No PSTI expression [45] Yes C79F [45] Rare - No PSTI expression [45] Yes -142T > C, -147A > G, -164G > C, -170G > A, -215G > A and -215G > T) was recently investigated by means of both luciferase reporter gene assay and electrophoretic mobility shift assay, using human pancreatic COLO-357 cells as an expression system. Login to comment 92 ABCC7 p.Arg75Gln The Whitcomb group recently reported that the coinheritance of CFTR R75Q and SPINK1 variants is significantly higher in patients with idiopathic chronic pancreatitis than in controls (8.75% vs. 0.38%). Login to comment 94 ABCC7 p.Arg75Gln However, the over-representation of the trans-heterozygosity for CFTR R75Q and SPINK1 variants in patients was challenged by Witt and colleagues [55], who argued that the contribution of CFTR to chronic pancreatitis had been overestimated in the previous studies. Login to comment