ABCMdb

ABCC7 p.Ala1087Pro

None has been submitted yet.

Publications

PMID: 15987793 [PubMed] Weiss FU et al: "Complete cystic fibrosis transmembrane conductance regulator gene sequencing in patients with idiopathic chronic pancreatitis and controls."

No. Sentence Comment

233 CFTR mutations in idiopathic pancreatitis www.gutjnl.com Three of the four compound heterozygous ICP patients carried one severe DF508 mutation (genotypes: DF508/ R117H, DF508/A1087P, DF508/D1152H) and one carried two mild mutations (S1235R/R668C). Login to comment
238 M348V and A1087P present novel molecular changes in the CFTR gene with so far undetermined consequences on CFTR function. Login to comment
239 A1087P affects the intracellular loop between the transmembrane domains M10 and M11 and is most probably a mild missense mutation whereas M348V is located in the sixth transmembrane domain of the protein, where the wild type sequence has been conserved during evolution. Login to comment
256 The reason why numbers for compound heterozygous ICP patients in these studies are diverse (4/67 = 6% in our study) may be due to differences Table 1 CFTR and SPINK1 sequence variations identified in 30 of the 67 ICP patients PatientSex CFTR mutation T allele TG repeats PSTI mutation 1 M DF508/R117H 7/7 9/10 -/- 2 W DF508/A1087P 7/9 10/11 -/- 3 M DF508/D1152H 7/9 10/10 -/- 4 M S1235R/R668C 7/7 11/12 -/- 5 M 2184insA/- 7/7 10/12 -/- 6 M R31C/- 7/7 10/11 -/- 7 M R75Q/- 7/7 11/11 -/- 8 M R347P/- 7/7 11/12 -/- 9 M S1235R/- 7/7 11/12 -/- 10 W S1235R/- 7/7 11/12 -/- 11 M G576A/- 7/7 10/10 -/- 12 W M348V/- 7/9 10/10 -/- 13 M V754M/- 7/7 10/11 -/- 14 M -/- 5/7 11/12 -/- 15 W -/- 5/7 11/12 -/- 16 M -/- 5/7 11/12 -/- 17 W -/- 5/9 11/12 -/- 18 M -/- 5/7 11/12 -/- 19 M -/- 5/7 10/10 -/- 20 W -/- 5/7 10/10 -/- 21 W -/- 5/7 11/12 N34S/- 22 W -/- 7/7 10/11 N34S/- 23 M -/- 7/9 10/11 N34S/- 24 M -/- 7/7 11/11 N34S/- 25 M -/- 7/7 11/11 N34S/- 26 W -/- 7/7 11/11 N34S/- 27 M -/- 7/7 11/11 N34S/- 28 W -/- 7/7 10/11 N34S/- 29 W -/- 7/7 11/11 P55S/- 30 W -/- 7/7 11/11 IVS3+2TC/- Table 2 CFTR sequence variations identified in 11 of 60 healthy controls Control group Number DF508/- 3 R117H/- 2 I148T/- 1 L997F/- 1 5T/12TG 1 5T/11TG 3 in patient recruitment, the catchment populations, or the stringency with which cystic fibrosis patients were excluded. Login to comment

PMID: 19359437 [PubMed] Weiss FU et al: "Functional characterisation of the CFTR mutations M348V and A1087P from patients with pancreatitis suggests functional interaction between CFTR monomers."

No. Sentence Comment

0 LETTERS Functional characterisation of the CFTR mutations M348V and A1087P from patients with pancreatitis suggests functional interaction between CFTR monomers In a recent study on the role of cystic fibrosis transmembrane conductance regulator (CFTR) mutations in idiopathic chronic pancreatitis (Gut 2005;54:1456-60) we sequenced the complete CFTR-coding region of 67 pancreatitis patients and 60 controls. Login to comment
2 Two patients with previously unknown CFTR mutations (M348V and A1087P) were identified, and their unexpected clinical course after conclusion of the trial prompted the functional studies below. Login to comment
5 The patient with the A1087P mutation was recruited to the study as a 19 year old with idiopathic chronic pancreatitis and exocrine pancreatic insufficiency. Login to comment
7 An ambiguous sweat chloride test together with the presence of a DF508 mutation (inherited from her healthy mother) and the novel A1087P mutation (inherited from her healthy father) suggest that this patient suffers from a mild variety of cystic fibrosis rather than from idiopathic chronic pancreatitis, as initially thought. Login to comment
10 In contrast, the residual Cl2 current of the A1087P mutant was only 6% (3%) (mean (SD), n = 9 of the wild-type CFTR, which is typical of a mutation associated with severe cystic fibrosis. Login to comment
11 In addition, the A1087P mutant acted as dominant-negative variant and reduced the activity of co-expressed wild-type CFTR by 78% (7%) (n = 6). Login to comment
16 The observed reduction of Cl2 and HCO3 2 fluxes without reduction of current by the M349V mutation may be related to impaired activation of other Cl2 and HCO3 2 transporters, such as members of the SLC26 Cl2 /HCO3 2 exchangers.2 The A1087P mutant supports minimal Cl2 and HCO3 2 transport and markedly inhibited the function of co-expressed wild-type CFTR. Login to comment
19 The residual CFTR function of the A1087P mutant may explain the late onset of cystic fibrosis symptoms in the second patient, its unusually mild clinical course and its original misclassification. Login to comment
20 The patient`s brother who inherited the A1087P but not the DF508 mutation has symptoms of neither pancreatitis nor cystic fibrosis. Login to comment
21 Another implication of the functional analysis of the A1087P mutant is that monomers of CFTR may affect each others` functions. Login to comment
22 The minimal functional unit of CFTR appears to be a monomer,3 but CFTR has also been shown to function as a dimer.4 Although, in vivo CFTR appears to function as a monomer, the dominant-negative function of the A1087P mutant would be consistent with functional interaction of CFTR monomers. Login to comment
24 Our findings regarding the A1087P mutant, on the other hand, suggest that this variant must be considered a severe cystic fibrosis mutation. Login to comment
25 The unusually mild clinical course of the A1087P mutation-affected patient and its misclassification in the original trial serve as a reminder that cystic fibrosis and pancreatitis can coexist and that a clear distinction between these CFTR-dependent disease entities is sometimes difficult. Login to comment

PMID: 25702115 [PubMed] Gee HY et al: "Analysis of conventional and unconventional trafficking of CFTR and other membrane proteins."

No. Sentence Comment

2366 Functional characterisation of the CFTR mutations M348V and A1087P from patients with pancreatitis suggests functional interaction between CFTR monomers. Login to comment