ABCMdb

PMID: 11025834

Wang X, Moylan B, Leopold DA, Kim J, Rubenstein RC, Togias A, Proud D, Zeitlin PL, Cutting GR
Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population.
JAMA. 2000 Oct 11;284(14):1814-9., 2000-10-11 [PubMed]

Sentences

No. Mutations Sentence Comment

11 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Results Eleven CRS patients were found to have a CF mutation (⌬F508, n=9; G542X, n=1; and N1303K, n=1). Login to comment 30 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr ABCC7 p.Phe508Cys ABCC7 p.Ile506Val ABCC7 p.Ile507Val Analysis of CFTR Genes Genomic DNA samples extracted from the blood of participants were screened for 16 mutations (R117H, 621+1G→T, R334W, R347P, A455E, ⌬I507, ⌬F508, 1717-1 G→A, G542X, S549N, G551D, R553X, R560T, 3849+10 Kb C→T, W1282X, and N1303K) that account for 85% of CF alleles in the white population using the multiplex reverse dot hybridization system (Roche Molecular Systems, Alameda, Calif).16,17 This test also identified the 5T, 7T, and 9T variants of the splice acceptor site in intron 8 and F508C, I507V, and I506V (exon 10) polymorphisms of the CFTR gene. Login to comment 46 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Eleven CRS patients were found to have CF mutations (TABLE 1); 9 had the common mutation, ⌬F508, 1 had G542X, and 1 had N1303K. Login to comment 53 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg75Gln ABCC7 p.Leu967Ser Using this technique, we previously demonstrated that at least 96% of mutations in the exons and flanking intron regions of the CFTR gene can be detected.16 A 97% sensitivity was achieved using 115 samples with previously identified mutations16 in this study.Sequenceanalysisofsampleswith anabnormalDGGEpatternidentifiedan R75Q mutation in the N1303K carrier and an L967S mutation in the G542X carrier. Login to comment 54 ABCC7 p.Arg75Gln ABCC7 p.Leu967Ser Neither R75Q or L967S is a CF-causing mutation (Cystic Fibrosis Mutation Data Base, http://www.genet .sickkids.on.ca/cftr/). Login to comment 59 ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Leu967Ser ABCC7 p.Leu967Ser Patient 1386 had changes in exon 10 (M470V), exon 15 (L967S), and exon 11 (G542X), and pedigree analysis was used to show that the M470V variant and the L967S variant segregated independently of G542X. Login to comment 66 ABCC7 p.Asn1303Lys The patient having 2 CF mutations (No. 1624) had an elevated sweat chloride concentration (102 mmol/L) (normal level, Ͻ60 mmol/L).20 The N1303K carrier patient (No. 1344) had 2 borderline and 1 elevated sweat chloride concentration measurements (55, 58, and 78 mmol/L), while the re- Table 1. Login to comment 67 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg75Gln ABCC7 p.Leu967Ser Cystic Fibrosis (CF) Mutations and Cystic Fibrosis Transmembrane Regulator (CFTR) Variants in Chronic Rhinosinusitis (CRS) Patients and Controls* CRS, No. (%) Non CRS, No. (%) P Value (n = 147) (n = 123) CF mutations ⌬F508/+ 1 2 ⌬F508/M470V 7 0 G542X/M470V, L967S 1 0 N1303K/+; M470V/M; R75Q/+† 1 0 (⌬F508/2789+5G→A)‡ 1 0 Frequency of CF carriers 10 (7) 2 (2) .04§ (n = 136) (n = 121) CFTR variants 5T Variant in non-CF carriers࿣ 5T/+ 11 (9) 6 (6) .25§ Codon 470 genotypes among non-CF carriers࿣ M/M 21 (16) 23 (19) M/V 55 (40) 64 (53) .03¶ V/V 60 (44) 34 (28) *Plus (+) indicates wildtype. Login to comment 84 ABCC7 p.Asn1303Lys ABCC7 p.Arg75Gln Cystic Fibrosis Transmembrane Regulator (CFTR) Genotypes and Clinical Features of Chronic Rhinosinusitis Patients Having a Cystic Fibrosis Mutation* Patient No. Sex CFTR Genotype Age of Onset, y Sinus Surgery, No. of Times Polyposis Pulmonary Status Gastrointestinal Status Sweat Chloride Concentration, mmol/L† Other Pertinent Clinical Features 1344 F N1303K/+; M470V/M; R75Q/+‡ Ͻ10 3 - Recurrent bronchitis Lactose intolerant 55, 58, 78 . Login to comment 87 ABCC7 p.Gly542* ABCC7 p.Leu967Ser 1386 M G542X/M470V, L967S 16 14 + Asthma, Pseudomonas aeruginosa pneumonia§ Normal Ͻ15 Fathered 3 children, genetically confirmed 1379 F ⌬F508/M470V Ͻ10 8 - Normal Normal 31 Problem conceiving 1380 M ⌬F508/M470V 59 2 + Asthma Normal 39 Fathered 2 children 1468 F ⌬F508/M470V 20 2 - Normal Normal 29 Problem conceiving 1509 F ⌬F508/M470V 26 None - Asthma Normal 21 . Login to comment 125 ABCC7 p.Arg75Gln ABCC7 p.Leu967Ser Indeed, in addition to CRS, patient 1344 had subtle sweat gland dysfunction and a history of bronchitis while patient 1386 had sputum infected with Pseudomonas aeruginosa, an organism common in CF patients but unusual in the general population.7 Both patients were found to carry mutations that are not associated with CF (R75Q and L967S). Login to comment