ABCMdb

PMID: 11589722

Walkowiak J, Herzig KH, Witt M, Pogorzelski A, Piotrowski R, Barra E, Sobczynska-Tomaszewska A, Trawinska-Bartnicka M, Strzykala K, Cichy W, Sands D, Rutkiewicz E, Krawczynski M
Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR mutation does not exclude pancreatic insufficiency.
Eur J Clin Invest. 2001 Sep;31(9):796-801., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg560Thr ABCC7 p.Glu217Gly Results Severe pancreatic insufficiency was associated with the presence of two CFTR gene mutations (DF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717±1G-A, R533X, W1282X, 621GT, 2183AAG, R560T, 2184insA and DI507, G551D, 895T) and mild insufficiency with the presence of at least one mutation (R117H, 3171insC, A155P2, 138insL, 296 1 1G-A, E92GK, E217G, 2789 1 5G-A. Login to comment 7 ABCC7 p.Arg334Trp However, in case of patients with genotype DF508/3849 1 10kbC-T, 1717±1GA/3849 1 10kbC-T as well as with DF508/R334W, both high and low elastase-1 concentrations were found. Login to comment 8 ABCC7 p.Arg347Pro Low E1 values were found in a patient with DF508/R347P genotype. Login to comment 51 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg560Thr ABCC7 p.Glu217Gly Results Among 394 genotyped CF patients, the following mutations on alleles were found (n): DF508 (464), 3849 1 10kbC-T (30), CFTR dele2,3(21 kB) (21), N1303K (15), G542X (12), 1717±1G-A (9), R533X (6), W1282X (6), 621 1 G-T (3), R117H (2), 3171insC (2), A155P2 (2), 2183AAG (2), R334W (2), 895T (2), 296 1 1G-A (2), E92GK (2), 138insL (1), E217G (1), 2789 1 5G-A (1), R347P (1), R560T (1), 2184insA (1), I507 (1), G551D (1). Login to comment 57 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg560Thr CFTR gene mutations were classified as `severe' (E1 , 96 mg g21 ) ± severely affecting pancreatic function (DF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717±1G-A, R533X, W1282X, 621 1 1G-T, 2183AAG, 895T, R560T, 2184insA, DI507, G551D) and `mild' (E1 . Login to comment 58 ABCC7 p.Arg117His ABCC7 p.Glu217Gly 156 mg g21 ) ± mildly affecting pancreatic function (R117H, 3171insC, A155P2, 296 1 1G-A, E92GK, 138insL, E217G, 2789 1 5G-A). Login to comment 60 ABCC7 p.Arg334Trp However, patients with DF508/ 3849 1 10kbC-T, 1717±1GA/3849 1 10kbC-T genotype as well as with DF508/R334W had both high and low E1 concentrations. Login to comment 61 ABCC7 p.Arg347Pro Low E1 concentrations were found in a patient with DF508/R347P genotype. Login to comment 81 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg560Thr ABCC7 p.Glu217Gly 500 DF508/3849 1 10kbC-T (17) 1 4 1 6 5 DF508/CFTR dele2,3(21kb) (15) 9 4 2 DF508/N1303K (10) 7 3 DF508/1717±1G-A (7) 5 2 DF508/G542X (7) 4 2 1 DF508/W1282X (5) 4 1 DF508/R553X (3) 3 DF508/R334W (2) 1 1 DF508/2183AAG (2) 2 DF508/R117H (1) 1 DF508/621GT (1) 1 DF508/R347P (1) 1 DF508/2184insA (1) 1 DF508/DI507 (1) 1 3849 1 10kbC-T/3849 1 10kbC-T (3) 3 N1303K/CFTR dele2,3(21kb) (2) 1 1 1717±1G-A/3849 1 10kbC-T (2) 1 1 3171insC/A155P2 (2) 1 1 296 1 1G-A/E92GK (2) 2 R117H/138insL (1) 1 W1282X/3849 1 10kbC-T (1) 1 N1303K/3849 1 10kbC-T (1) 1 CFTR dele2,3(21kb)/3849 1 10kbC-T (1) 1 R553X/G542X (1) 1 621 1 1G-T/621 1 1G-T (1) 1 G542X/M (4) 2 2 CFTR dele 2,3(21kb)/M (1) 1 2 3849 1 10kbC-T/M (2) 1 1 R533X/M (2) 2 N1303K/M (2) 2 895T/M (2) 1 1 E217G/M (1) 1 G551D/M (1) 1 R560T/M (1) 1 2789 1 5G-A/M (1) 1 Total (109) 44 21 10 4 12 18 M, unidentified mutation. Login to comment 85 ABCC7 p.Gly551Asp ABCC7 p.Ser549Asn ABCC7 p.Arg347Trp Previously, it has been shown that pancreatic insufficiency was related to mutation G551D and pancreatic sufficiency to R347W and S549N [11]. Login to comment 86 ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Gly542* ABCC7 p.Ile148Thr ABCC7 p.Gln493* ABCC7 p.Val520Phe ABCC7 p.Arg560Thr ABCC7 p.Gly480Cys Kristidis et al. [10] reported that pancreatic insufficiency strongly correlates also with two alleles of DI507, Q493X, G542X, R553X, W1282X, 621 1 1G-T, 1717±1G-A, 556delA, 3659delC, I148T, G480C, V520F and R560T while one or two mutations such as R117H, R334W, A455E, and P574H were correlated with a pancreatic sufficient phenotype. Login to comment 88 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* An international Cystic Fibrosis Genotype-Phenotype Consortium [25] evaluated DF508 homozygotes and seven of the most common DF508 compound heterozygotes (G542X, R553X, N1303K, W1282X, 1717±1G-A, 621 1 1GT, R117H). Login to comment 90 ABCC7 p.Asn1303Lys ABCC7 p.Trp846* ABCC7 p.Glu827* N1303K was found to be a severe mutation in addition to E827X, W846X, while 4382delA, 3272±26G-A and 3849 1 10kbCT were assessed as mild ones [8]. Login to comment 91 ABCC7 p.Glu217Gly Based on our findings we are able to classify additional mutations as `severe' (CFTR dele2,3(21kb), 2183AAG, 895T, 2184insA) and `mild' (3171insC, A155P2, 138insL, 296 1 1G-A, E92GK, E217G, 2789 1 5G-A). Login to comment 93 ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro In contrast to the results of the above mentioned studies [8,10,11], our patients with the mutations for 3849 1 10kbC-T (class V), R334W and R347P (class IV) combined with DF508 or 1717±1G-A presented also as pancreatic insufficient. Login to comment