ABCMdb

PMID: 11158459

Wine JJ, Kuo E, Hurlock G, Moss RB
Comprehensive mutation screening in a cystic fibrosis center.
Pediatrics. 2001 Feb;107(2):280-6., [PubMed]

Sentences

No. Mutations Sentence Comment

16 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Pro67Leu ABCC7 p.Gly970Asp ABCC7 p.Arg75* ABCC7 p.Ser13Phe ABCC7 p.Leu1093Pro ABCC7 p.Ser492Phe Mutations detected in both groups included 7 missense mutations (S13F, P67L, G98R, S492F, G970D, L1093P, N1303K) and 9 deletion, frameshift, nonsense or splicing mutations (R75X, G542X, ⌬F508, 451-458⌬8 bp, 5T, 663⌬T, exon 13 frameshift, 1261؉1G3A and 3272-26A3G). Login to comment 17 ABCC7 p.Gly970Asp ABCC7 p.Leu1093Pro Three of these mutations were novel (G970D, L1093P, and 451-458⌬8 bp1). Login to comment 86 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gln493* ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Ser1455* Mutations in the Stanford CF Mutation Database After Screening With the Genzyme70 Assay Mutation n % n % ⌬F508 353 67.11% 353 67.11% Splice mutations 16 3.04% 621ϩ1 G3T 5 0.95% 1717-1 G3A 5 0.95% 2789ϩ5 G3A 1 0.19% 1898ϩ1 G3A 1 0.19% 3849ϩ10 kb C3T 4 0.76% Stop mutations 31 5.89% Q493X 1 0.19% G542X 13 2.47% R553X 4 0.76% R1162X 1 0.19% W1282X 10 1.90% S1455X 2 0.38% Insertions/deletions 9 1.71% 681 del C 1 0.19% 2184 del A 2 0.38% 3859 del C 5 0.95% 3905 ins T 1 0.19% Missense mutations 33 6.27% G85E 4 0.76% R117H 3 0.57% R334W 6 1.14% G551D 14 2.66% R560T 3 0.57% N1303K 3 0.57% Unknown mutations 84 15.97% 84 15.97% Total 526 100.00% 526 100.00% ARTICLES tients with positive sweat tests were selected for SSCP/HA analysis based on clinical status, ethnicity, and previous screening with the Genzyme70 assay. Login to comment 100 ABCC7 p.Pro67Leu After screening with SSCP/HA, 2 mutations, P67L and 1261ϩ1G3A, were detected in another patient who also had the highest sweat chloride value in this group (48 mM). Login to comment 115 ABCC7 p.Asn1303Lys ABCC7 p.Gly970Asp ABCC7 p.Arg75* ABCC7 p.Leu1093Pro Mutation Detection in 10 Participants With Positive Sweat Chloride Values I.D. Pancreatic Function Mutation Status Discovered Mutations (Novel) Polymorphisms SP1 PI N1303K/unk* L1093P (17b), M470V (10)* SP2 PI unk*/unk* S13F (exon1) 2184 ins A (exon 13) GATT7/7, 2694 T/G SP3 PS unk*/unk* ⌬451-458 (4); G970D (16) GATT7/6, 2694 T/G SP4 PS unk*/unk* R75X (3), G98R (4) GATT7/7, 492 G/A SP5 PS unk*/unk 3272-26A/G (17b) M470V/M470V (10) SP6 PI/PS (mild) ⌬F508/unk None found - SP7 PI ⌬F508/unk None found GATT6/7,1001ϩ11C/T (6b), M470V (10) SP8 PI unk*/unk S492F (10) GATT7/7 GT11/11 M470V/M470V SP9 PI ⌬F508/unk None found - SP10 PI unk*/unk* 663 ⌬T/663 ⌬T GATT6/6, 2694T3G Column labeled Pancreatic Function indicates the need for dietary supplementation with pancreatic enzymes. Login to comment 135 ABCC7 p.Gly970Asp ABCC7 p.Leu1093Pro Novel mutations ⌬451-458 and G970D were reported separately1; novel mutation L1093P has been submitted for publication. Login to comment 155 ABCC7 p.Gly542* ABCC7 p.Pro67Leu PS none - SN3 unk/unk 10-15 PS none GATT6/6, 1001ϩ11 C3T, TG10, T9 homozygous all SN4 unk/unk 25 PI None M470V (10), (GT)11/10 GATT7/7, 1896ϩ152 A/T (I12); 2694T/G (14a), 4521G3A (24) SN5 G542X unk 25 PS none M470V (10), TG11, T7 SN6 unk*/unk* 48 PS P67L (3) 1261ϩIG3A (I13) 1898ϩ174 ins A (I12), 2694T3G (14a) 4521G3A (24) 1812-3 ins T, (I11), homozygous SN7 unk/unk 40 PS None found - Notation as for Table 1. Login to comment 176 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp Stop mutations account for about 7% of the patients at this center, and some of these mutations may be amenable to correction by encouraging read-through with agents such as aminoglycosides.21,22 The mutation G551D, which interferes with efficient adenosine triphosphate gating of CFTR, accounts for ϳ4% of our patients, and experiments indicate that the activity of G551D-CFTR can be increased with the isoflavone genistein.23 Whereas these kinds of mutations are relatively rare, mutations that lead to improper folding of CFTR, such as ⌬F508, are responsible for the great majority of CF.24 The molecular basis for these processes is under intense investigation,25 and strategies for inducing an increased proportion of properly folded, functional molecules at the plasma membrane have achieved success in vitro26-28. Login to comment