ABCC7 p.Met281Thr
| ClinVar: |
c.842T>C
,
p.Met281Thr
?
, not provided
|
| CF databases: |
c.842T>C
,
p.Met281Thr
(CFTR1)
?
, This change has been detected by SSCP/HD analysis and direct sequencing.
|
| Predicted by SNAP2: | A: D (66%), C: D (59%), D: D (85%), E: D (75%), F: N (93%), G: D (80%), H: D (80%), I: N (72%), K: D (85%), L: N (78%), N: D (75%), P: D (85%), Q: D (71%), R: D (85%), S: D (75%), T: D (75%), V: N (72%), W: D (71%), Y: D (66%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, L: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: N, Y: N, |
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[hide] Different CFTR mutational spectrum in alcoholic an... Pancreas. 2004 May;28(4):374-9. Casals T, Aparisi L, Martinez-Costa C, Gimenez J, Ramos MD, Mora J, Diaz J, Boadas J, Estivill X, Farre A
Different CFTR mutational spectrum in alcoholic and idiopathic chronic pancreatitis?
Pancreas. 2004 May;28(4):374-9., [PMID:15097853]
Abstract [show]
OBJECTIVE: Cystic fibrosis transmembrane conductance regulator (CFTR) mutations are responsible for cystic fibrosis (CF) and have been postulated as a predisposing risk factor to chronic pancreatitis (CP), but controversial results demand additional support. We have therefore investigated the role of the CFTR gene in a cohort of 68 CP patients. METHODS: We have performed the CFTR gene analysis using 2 screening techniques. Fragments showing abnormal migration patterns were characterized by sequencing. Patients were classified in alcoholic (ACP) (n = 37) and idiopathic (ICP) (n = 31) chronic pancreatitis. Clinical features of CP and CF were evaluated. RESULTS: Sixteen mutations/variants were identified in 27 patients (40%), most of them (35%) presenting a single CFTR mutant gene. The 1716G/A variant showed the highest frequency accounting for 22% in ICP and 5% in ACP, in contrast with other more common mutations such as F508del found in 8% of ACP and the 5T variant identified in 7% of patients. Acute pancreatitis, abdominal pain, tobacco, pancreatic calcifications, and pancreatic pseudocysts showed significant higher values in ACP than ICP patients. No significant differences were found between patients with and without CFTR mutations. CONCLUSIONS: Apart from reinforcing previous findings our data highlight the increased susceptibility of CFTR heterozygous to developing CP. Heterozygosity, combined with other factors, places these individuals at greater risk.
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No. Sentence Comment
48 Twelve out of 16 changes observed (75%) were missense mutations/variants, the M281T a T→C substitution at nucleotide 974 is reported for the first time in this work.
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ABCC7 p.Met281Thr 15097853:48:78
status: NEW63 Time Years BMI Alcohol Alcohol Time Years Tobacco Pancreatic Features Hepatobiliary Disease CFTR Genotype Sweat Test mmol/L FEV1/FVC % Predicted Male Fertility Alcoholic Chronic Pancreatitis (n = 15) 1 M/52 15 24.5 110g/d 27 yes AP, P, Ps, DM, PI Chronic hepatitisa F508del/S1235R 18 105/107 yes 2 M/72 15 23.4 85g/d 22 yes AP, P, C, PS no F508del/1716G/A 72 90/104 yes 3 M/53 10 21.9 135g/d 20 yes P, C, DM, PI no F508del/- 54 71/89 yes 4 M/64 18 20.7 250g/d 27 yes AP, P, C, Ps, DM, PI cirrhosis, lithiasis W1282X/- 68 71/78 unproved 5 M/44 13 22.0 95g/d 6 yes AP, P, C, Ps, DM, PI lithiasis R170C/- 16 105/111 yes 6 M/62 12 22.1 >60g/d >5 yes AP, P, C, Ps, DM, PS no R258G/- 82 73/82 yes 7 M/38 9 18.0 210g/d 15 yes AP, P, C, Ps, PS no M281T/- 62 132/126 yes 8 M/40 11 - >60g/d >5 yes AP, P, C, Ps, PS lithiasis R297Q/- 46 103/99 yes 9 M/42 2 21.4 150g/d 20 yes AP, P, C, Ps, PS no 1716G/A/- 19 93/102 yes 10 M/44 3 22.2 95g/d 22 yes AP, P, DM, PS no R668C/- 58 105/102 yes 11 M/59 6 21.8 90g/d 18 yes PS lithiasis L997F/- 85 69/84 nd 12 M/72 16 - >60g/d >5 no P, C, DM, PI lithiasis R1162L/- - - yes 13 M/35 8 21.0 90g/d 7 yes AP, P, C, PS no 5T-12TG-V470/- 13 106/114 unproved 14 M/60 14 28.0 80g/d 20 no AP, P, C, Ps, DM, PI no 5T-11TG/- 28 80/77 yes 15 M/65 12 24.4 100g/d 23 yes AP, P, C, DM, PS no 5T-11TG/ 40 86/110 yes Idiopathic Chronic Pancreatitis (n = 12) 16 M/21 5 - no - yes AP, P, PS no 1716G/A/R170H 40 normal yes 17 M/59 4 24.2 no - no PS chronic hepatitisb 1716G/A/- 40 146/128 yes 18 M/63 14 21.4 no - no DM, PI no 1716G/A/- 34 144/126 yes 19 M/70 18 19.9 no - yes AP, P, DM, PI chronic hepatitisa 1716G/A/- 60 36/47 yes 20 M/65 1 27.7 no - yes P, Ps, DM, PI no 1716G/A/- 38 79/78 yes 21 M/76 8 24.1 no - no AP, P, DM, PS no 1716G/A/- 60 81/109 yes 22 M/25 2 25.0 no - yes AP, P, PS no 1716G/A/- 48 94/86 nd 23 F/42 10 22.6 no - yes P, C, PS lithiasis P205S/- 72 111/109 - 24 F/81 21 34.6 no - no P, C, DM, PI lithiasis D443Y+G+R*/- 42 121/108 - 25 F/72 8 23.3 no - yes AP, C, PS no L997F/- 40 100/93 - 26 M/9 2 19.2 no - no AP, P, PS no 5T-11TG/- 30 101/110 nd 27 M/63 6 - no - no C, DM, PI cirrhosis 5T-11TG/- - - yes a C virus hepatitis.
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ABCC7 p.Met281Thr 15097853:63:739
status: NEW[hide] Independent contribution of common CFTR variants t... Pancreas. 2010 Mar;39(2):209-15. de Cid R, Ramos MD, Aparisi L, Garcia C, Mora J, Estivill X, Farre A, Casals T
Independent contribution of common CFTR variants to chronic pancreatitis.
Pancreas. 2010 Mar;39(2):209-15., [PMID:19812525]
Abstract [show]
OBJECTIVE: We have assessed whether CFTR gene has a major impact on chronic pancreatitis (CP) pathogenesis than that provided by the CFTR mutations. For this aim, we have evaluated clinical parameters, CFTR mutations, and 3 potential regulatory CFTR variants (coding single-nucleotide polymorphisms): c.1540A>G, c.2694T>G, and c.4521G>A. METHODS: CFTR gene analysis was performed in a cohort of 136 CP patients and 93 controls from Spanish population using current scanning techniques (single-strand conformation polymorphism/heteroduplex, denaturing gradient gel electrophoresis, and denaturing high-performance liquid chromatography) and direct sequencing. RESULTS: A higher frequency of CFTR mutations were observed in patients (39%) than in controls (15%; P < or = 0.001), differences being mostly attributable to the prevalence of the cystic fibrosis (CF)-causing mutations (P = 0.009). The analysis of variants has shown statistically significant differences between patients and controls for c.4521G>A (Pcorrected = 0.036). Furthermore, the multi-marker analysis revealed that the 1540A;2694G;4521A (AGA) haplotype was more prevalent in CP than controls (Pcorrected = 0.042). Remarkably, this association was unrelated to CF-causing mutations (P = 0.006). CONCLUSIONS: Our results corroborate the higher susceptibility of CF carriers to CP and, furthermore, suggest that the AGA haplotype could contribute to an increased risk in the development of CP irrespective of other CF-causing mutations.
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No. Sentence Comment
81 CFTR Genotypes in Chronic Pancreatitis Patients and General Population Pt/Phenotype CFTR Genotype Pt/Phenotype CFTR Genotype 1/ACP F508del† , I1027T/j 19/ACP* R668C/j 2/ACP* F508del† /j 20/ACP D836Y/j 3/ACP F508del† , I1027T/Y1014C 21/ACP* L997F† /j 4/ACP F508del† /1716G9A 22/ACP* R1162L/j 5/ACP* F508del† /1716G9A 23/ACP 5T-11TG/j 6/ACP* F508del† /S1235R 24/ACP 5T-11TG/j 7/ACP G542X† /j 25/ACP 5T-11TG/j 8/ACP* W1282X† /j 26/ACP* 5T-11TG/j 9/ACP 5T-12TG† /5T-11TG 27/ACP* 5T-11TG/j 10/ACP* 5T-12TG† /j 28/ACP 1716G9A/4374+13A9G 11/ACP R75Q/j 29/ACP 1716G9A/j 12/ACP R75Q/j 30/ACP 1716G9A/j 13/ACP Y122C/Y122C 31/ACP 1716G9A/j 14/ACP* R170C/j 32/ACP 1716G9A/j 15/ACP* R258G/j 33/ACP* 1716G9A/j 16/ACP* M281T/j 34/ACP 2377C9T/j 17/ACP* R297Q† /- 35/ACP* 2377C9T/j 18/ACP T351S/- 36/ACP 3499+37G9A/j 1/ICP F508del† /- 10/ICP* 1716G9A/j 2/ICP D443Y,G576A,R668C† /j 11/ICP* 1716G9A/j 3/ICP* D443Y,G576A,R668C† /j 12/ICP 1716G9A/j 4/ICP* P205S† /j 13/ICP* 1716G9A/j 5/ICP* L997F† /j 14/ICP* 1716G9A/j 6/ICP* R170H/1716G9A 15/ICP* 1716G9A/j 7/ICP 109A9G/j 16/ICP* 1716G9A/j 8/ICP* 5T-11TG/j 17/ICP 1716G9A/j 9/ICP* 5T-11TG/j 1/GP 5T-12TG† /j 8/GP 1716G9A/j 2/GP 5T-12TG† /j 9/GP 1716G9A/j 3/GP A534E† /j 10/GP 1716G/A/j 4/GP 5T-11TG/V562I 11/GP 1716G9A/j 5/GP 5T-11TG/j 12/GP 1716G9A/j 6/GP 5T-11TG/j 13/GP 3690A9G/j 7/GP 1716G9A/j 14/GP 3690A9G/j Corresponding mutation nomenclature (Human Genome Variation Society and Cystic Fibrosis Mutation Data Base): c.1584G9A (1716G9A), c.1210-7_1210-6delTT (5T), 1210-34_1210-13TG (11TG), g.-23A9G (109A9G), c.4242+13A9G (4374+13A9G), c.2245C9T (2377C9T), c.3367+ 37G9A (3499+37G9A), and c.3558A9G (3690A9G).
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ABCC7 p.Met281Thr 19812525:81:781
status: NEW