ABCC7 p.Leu327Arg
| CF databases: |
c.980T>G
,
p.Leu327Arg
(CFTR1)
?
, This mutation is a substitution of T to G at position 1112 in nucleotide sequence and causes the replacement of a leucine by arginine residue in codon 327. This variation was observed by SSCP analysis during screening of CF samples for mutations. We are currently investigating wheter or not this alteration is a mutation or polymorphism.
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| Predicted by SNAP2: | A: N (53%), C: N (61%), D: D (80%), E: D (71%), F: N (87%), G: D (71%), H: D (66%), I: N (72%), K: D (63%), M: N (72%), N: D (71%), P: D (80%), Q: D (63%), R: D (75%), S: D (63%), T: D (59%), V: N (93%), W: D (63%), Y: D (59%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: N, M: N, N: D, P: D, Q: N, R: D, S: D, T: N, V: N, W: D, Y: N, |
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[hide] Molecular basis of hereditary pancreatitis. Eur J Hum Genet. 2000 Jul;8(7):473-9. Chen JM, Ferec C
Molecular basis of hereditary pancreatitis.
Eur J Hum Genet. 2000 Jul;8(7):473-9., [PMID:10909845]
Abstract [show]
Hereditary pancreatitis (HP) is an autosomal dominant disease. Two heterozygous missense mutations, R122H (R117H) and N29I (N21I), in the cationic trypsinogen gene have been clearly associated with HP. The 'self-destruct' model proposed for the R122H mutation is discussed in connection with the existing theory of pancreatitis, and the basic biochemistry and physiology of trypsinogen, with particular reference to R122 as the primary autolysis site of the cationic trypsinogen. Two different genetic mechanisms are identified which cause the R122H mutation, and gene conversion is the likely cause of the N29I mutation. A unifying model, which highlights an indirect impairment on the R122 autolysis site is hypothesised for the N29I mutation. Possible predisposition to pancreatitis by additional DNA variants in the gene, such as the A16V signal peptide cleavage site mutation and the K23R activation peptide cleavage site mutation is suspected, but not proven. Evidence of genetic heterogeneity of HP is reviewed and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations detected in HP families are re-evaluated. Finally, large scale association studies are expected to clarify the additional variants' role in pancreatitis and to identify new HP genes.
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No. Sentence Comment
81 It is worth pointing out that in 1996, the same year the identification of the cationic trypsinogen gene was associated with HP, mutations in the CFTR gene were reported to be detected in HP families.54 Of the two new mutations identified, a heterozygous L327R was found to segregate with the disease in one family.
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ABCC7 p.Leu327Arg 10909845:81:255
status: NEW84 Analogous with other atypical diseases of CF, including congenital absence of the vas deferens, chronic bronchitis and sinusitis with nasal polyposis, sporadic chronic pancreatitis with abnormal CFTR alleles was referred to as a monosymptomatic form of CF.57 These observations prompted us to re-evaluate the role of the L327R missense mutation in the CFTR gene identified in a single HP family.54 There could be three explanations: first, this substitution is indeed a disease-causing mutation.
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ABCC7 p.Leu327Arg 10909845:84:321
status: NEW86 Second, the L327R substitution represents a mere coincidence, provided that it does not have any phenotype-modifying effect on the disease.
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ABCC7 p.Leu327Arg 10909845:86:12
status: NEW[hide] Genetic testing in acute and chronic pancreatitis. Curr Gastroenterol Rep. 2001 Apr;3(2):115-20. Rolston RK, Kant JA
Genetic testing in acute and chronic pancreatitis.
Curr Gastroenterol Rep. 2001 Apr;3(2):115-20., [PMID:11276378]
Abstract [show]
Hereditary pancreatitis (HP) is clinically indistinguishable from pancreatitis with other causes. Patients with HP have an increased chance of developing pancreatitis. Mutations in the cationic trypsinogen gene appear to cause most HP, although there is evidence for mild genetic heterogeneity with defects in other genes. Trypsin stabilization and protection from autolysis appear to play a central role in the pathogenesis of pancreatitis. The role of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) as well as the pancreatic secretory trypsin inhibitor (PSTI) in patients with pancreatitis is intriguing but as yet incompletely understood. Genetic testing may help to identify and manage patients with HP. Healthcare professionals should understand the elements necessary for obtaining informed consent for patients undergoing these tests, the limits in interpreting test results, and the psychosocial issues that may arise from genetic testing.
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65 Chen and Ferec [29••], evaluating the role of the L327R missense mutation in the CFTR gene in a single family with hereditary pancreatitis postulated three possible mechanisms: 1) L327R causes monosymptomatic CF, the primary manifestation of which is pancreatitis; 2) The CFTR alteration is coincidental, and an unidentified disease-causing mutation probably lies in cationic trypsinogen; and 3) CFTR may act as a modifier gene in the pathogenesis of hereditary pancreatitis.
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ABCC7 p.Leu327Arg 11276378:65:64
status: NEWX
ABCC7 p.Leu327Arg 11276378:65:194
status: NEW[hide] Genetics of chronic pancreatitis. J Pediatr Gastroenterol Nutr. 2002 Feb;34(2):125-36. Witt H, Becker M
Genetics of chronic pancreatitis.
J Pediatr Gastroenterol Nutr. 2002 Feb;34(2):125-36., [PMID:11840029]
Abstract [show]
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No. Sentence Comment
223 One of these mutations, L327R, segregated with the disease within the family.
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ABCC7 p.Leu327Arg 11840029:223:24
status: NEW[hide] Sensitivity of single-strand conformation polymorp... Hum Mol Genet. 1994 May;3(5):801-7. Ravnik-Glavac M, Glavac D, Dean M
Sensitivity of single-strand conformation polymorphism and heteroduplex method for mutation detection in the cystic fibrosis gene.
Hum Mol Genet. 1994 May;3(5):801-7., [PMID:7521710]
Abstract [show]
The gene responsible for cystic fibrosis (CF) contains 27 coding exons and more than 300 independent mutations have been identified. An efficient and optimized strategy is required to identify additional mutations and/or to screen patient samples for the presence of known mutations. We have tested several different conditions for performing single-stranded conformation polymorphism (SSCP) analysis in order to determine the efficiency of the method and to identify the optimum conditions for mutation detection. Each exon and corresponding exon boundaries were amplified. A panel of 134 known CF mutations were used to test the efficiency of detection of mutations. The SSCP conditions were varied by altering the percentage and cross-linking of the acrylamide, employing MDE (an acrylamide substitute), and by adding sucrose and glycerol. The presence of heteroduplexes could be detected on most gels and in some cases contributed to the ability to distinguish certain mutations. Each analysis condition detected 75-98% of the mutations, and all of the mutations could be detected by at least one condition. Therefore, an optimized SSCP analysis can be used to efficiently screen for mutations in a large gene.
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No. Sentence Comment
77 Mutations L327R, R347P and R352Q were better distinguished from wild type on gel with higher acrylamide concentration.
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ABCC7 p.Leu327Arg 7521710:77:10
status: NEW121 1078delT (35), L327R (Ravnik-Glavac a al., unpublished), R334W (36), D36K (31), R347L (26), R347P (14), A349V (26), R352Q (30), 1221delCT (34); Exon 8: W401X (31), 1342-1G-C (25); Exon 9: G458V (37), 1525 -1G-A (38); Exon 10: S492F (34), Q493X (39), 1609delCA (40,17), deltaI507 (39,41), deltaF5O8 (3), 1717-1G-A (39,42); Exon 11: G542X (39), S549N, G551D, R553X (43), R553Q (44), A559T (43), R560K (Fine et al., pers. comm.), R560T (39); Exon 12: Y563N (39), 1833delT (Schwartz et al., pers. comm.), P574H (39), 1898 + 1G-C (31), 1898+3A-G (Ferrari et al., pers. comm.); Exon 13: G628R(G-C) (31), Q685X (Firec et al., pers. comm.), K716X (26), L719X (Dork etal., pers. comm.), 2522insC (15), 2556insAT (45), E827X (34); Exon 14a: E831X (Ffrec et al., pers. comm.), R851X (29), 2721delll (31), C866Y (Audrezet et al., pers. comm.); Exon 14b: 2789+5G-A (Highsmith et al., pers. comm.); Exon 15: 2907denT (21), 2991del32 (Dark and TQmmler, pers. comm.), G970R (31); Exon 16: S977P, 3100insA (D6rk et al., pers. comm.); Exon 17a: I1005R (Dork and TQmmler, pers. comm.), 3272-1G-A (46); Exon 17b: H1054D (F6rec et al., pers. comm.), G1061R (Fdrec et al., pers. comm.), 332Oins5, R1066H, A1067T (34), R1066L (Fe"rec etal., pers. comm.), R1070Q (46), E1104X (Zielenski el al., pers. comm.), 3359delCT (46), L1077P (Bozon « a/., pers. comm.), H1085R (46), Y1092X (Bozon etal., pers. comm.), W1098R, M1101K (Zielenski et al., pers. comm.); Exon 18: D1152H (Highsmith et al., pers. comm.); Exon 19:R1162X (36), 3659delC (39), 3662delA (25), 3667del4 (Chillon et al., pers. comm.), 3737ddA (35), 3821ddT (15), I1234V (35), S1235R (31), Q1238X (26), 3849G-A (25), 385O-3T-G (38); Exon20:3860ins31 (Chillon etal., pers. comm.), S1255X (47), 3898insC (26), 3905insT (Malik et al., pers. comm.), D127ON (48), W1282X (49), Q1291R (Dork et al., pers. comm.), Exon 21: N1303H (35), N13O3K (50), W1316X (43); Exon 22: 11328L/4116delA (Dork and TQmmler, pers. comm.), E1371X (25); Exon 23: 4374+ 1G-T (38); Exon 24: 4382delA (Claustres et al., pers. comm.).
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ABCC7 p.Leu327Arg 7521710:121:15
status: NEW