ABCMdb

PMID: 17035430

Ziedalski TM, Kao PN, Henig NR, Jacobs SS, Ruoss SJ
Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection.
Chest. 2006 Oct;130(4):995-1002., [PubMed]

Sentences

No. Mutations Sentence Comment

10 ABCC7 p.Arg75Gln The frequency of CFTR mutations was elevated above that expected in the general population: heterozygous ⌬F508 (12% vs 3%), R75Q (14% vs 1%), and intron 8 5T (17% vs 5 to 10%). Login to comment 11 ABCC7 p.Trp1282* ABCC7 p.Gly542* ABCC7 p.Arg668Cys ABCC7 p.Ile1027Thr ABCC7 p.Arg1162Leu ABCC7 p.Val456Ala ABCC7 p.Leu183Ile Other known CFTR mutations identified were V456A, G542X, R668C, I1027T, D1152, R1162L, W1282X, and L183I. Login to comment 12 ABCC7 p.Cys1344Ser ABCC7 p.Phe650Leu Three novel CFTR mutations were identified: A394V, F650L, and C1344S. Login to comment 79 ABCC7 p.Trp1282* ABCC7 p.Gly542* ABCC7 p.Arg75Gln ABCC7 p.Asp1152His ABCC7 p.Ile1027Thr ABCC7 p.Phe650Leu Other identified mutations included R75Q, G542X, V4566A, D1152H, F650L, I1027T, W1282X, and the intron 8 polymorphism IVS 8 5T. Login to comment 81 ABCC7 p.Arg75Gln Only two subjects had a known pathologic CFTR mutation (patient 15, R75Q; patient 18, IVS8 5T). Login to comment 85 ABCC7 p.Arg75Gln R75Q was the most prevalent mutation (n ϭ 5), followed by the IVS 8 5T polymorphism (n ϭ 5) and ⌬F508 (n ϭ 2). Login to comment 86 ABCC7 p.Cys1344Ser ABCC7 p.Phe650Leu We also identified three novel CFTR mutations, each in a separate patient with a normal sweat chloride concentration: A394V, C1344S, and F650L. Login to comment 87 ABCC7 p.Leu183Ile A fourth mutation (L183I) was found that was thought to be novel, but in the course of manuscript preparation and review this mutation was found to have been previously reported. Login to comment 89 ABCC7 p.Arg75Gln Of interest, the R75Q mutation was detected in seven subjects (frequency, 14%), while ⌬F508 mutations were found in six subjects (frequency, 12%). Login to comment 94 ABCC7 p.Trp1282* ABCC7 p.Gly542* ABCC7 p.Arg75Gln ABCC7 p.Asp1152His ABCC7 p.Ile1027Thr ABCC7 p.Val456Ala Comparison of pulmonary function test data did not demonstrate significant differences between the Table 1-Subjects With Diagnosis of CF* Patient No. Age, yr Sex Bronch NTM† Other Infection‡ CFTR Mutations M470V Alleles IVS8 PolyT§ Sweat Chloride Level, mEq/dL 1 63 F Y MAC, Mch ⌬F508, I1027T 1 7T/9T 41 2 58 F Y MAC 2 7T/7T 65 3 66 F Y MAC, Mka PA 1 7T/7T 70 4 62 F Y MAC R75Q 2 5T/7T 67 5 53 F Y MAC G542X 0 5T/7T 60 6 74 F Y MAC SA ⌬F508, D1152H 1 9T/9T 46 7 33 F Y N PA ⌬F508, V456A 1 9T/9T 74 8 49 M Y N 1 7T/7T 77 9 73 F Y N S malto W1282X 1 7T/7T 63 10 52 F N Msi 2 2 7T/7T 68 *Bronch ϭ bronchiectasis (Bronch); F ϭ female; M ϭ male; Y ϭ yes; N ϭ no. Login to comment 99 ABCC7 p.Arg75Gln Table 2-Subjects With Indeterminate Sweat Chloride Concentrations (40 to 60 mEq/dL)* Patient No. Age, yr Sex Bronch NTM† Other Infection CFTR Mutations M470V Alleles IVS8 PolyT Sweat Chloride Level, mEq/dL 11 60 F Y Mch, Mgo 2 7T/7T 40 12 68 F Y MAC 1 7T/7T 41 13 62 F Y MAC, Mch, Mgo 2 7T/7T 46 14 81 F Y MAC 2 7T/7T 49 15 65 F Y MAC R75Q 1 9T/9T 51 16 72 F Y MAC 2 7T/7T 53 17 62 F Y MAC 2 9T/9T 55 18 48 F Y 0 5T/7T 42 *See Table 1 for expansion of abbreviations. Login to comment 107 ABCC7 p.Arg75Gln Third, we have identified added novel CFTR mutations in this adult population, as well as an unusually high prevalence of typically infrequent mutations (eg, R75Q) in this population. Login to comment 113 ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Arg1162Leu ABCC7 p.Ala209Ser ABCC7 p.Cys1344Ser ABCC7 p.Leu183Ile ABCC7 p.Phe650Leu In contrast to Table 3-Subjects With Normal Sweat Chloride Concentrations (< 40 mEq/dL)* Patient No. Age, yr Sex Bronch NTM† Other Infection‡ CFTR Mutations M470V Alleles IVS8 PolyT Sweat Chloride, mEq/dL 19 40 F Y Mab 1 7T/7T 19 20 41 F Y MAC 1 7T/7T 20 21 74 F Y MAC, Mgo Asp, Noc ⌬F508 1 7T/9T 22 22 28 M Y MAC L183I 1 7T/7T 23 23 49 F Y MAC 1 7T/7T 25 24 58 M Y MAC, Mfo 1 5T/7T 25 25 76 F Y MAC SA A394V 2 5T/9T 26 26 79 F Y MAC 1 7T/7T 27 27 58 F Y MAC R75Q 1 7T/7T 28 28 78 F Y MAC PA 1 7T/9T 31 29 64 F Y MAC 1 5T/9T 31 30 57 F Y MAC, Mxe R75Q 2 7T/7T 34 31 81 F Y MAC, Mmu R668C 1 7T/7T 34 32 82 F Y N PA F650L 1 5T/9T 33 33 69 F Y MAC, Mch, Mab PA ⌬F508 0 7T/9T 35 34 81 F Y MAC C1344S 2 7T/7T 38 35 72 F Y MAC R75Q 2 7T/7T 38 36 55 M Y N ⌬F508 1 7T/7T 21 37 61 F Y N 0 7T/9T 20 38 42 F Y N 1 9T/9T 21 39 50 M Y N PA, SA, Asp 1 5T/7T 22 40 71 M Y N 2 7T/7T 23 41 83 F Y N 2 7T/7T 23 42 46 M Y N 2 7T/7T 25 43 49 F Y N R75Q 2 7T/7T 33 44 48 F Y N PA R75Q 2 9T/9T 35 45 76 F Y N R1162L 1 7T/7T 35 46 67 M Y N A209S 0 9T/9T 36 47 46 F Y N 1 7T/7T 36 48 63 F N MAC 1 9T/9T § 49 60 F N MAC 1 7T/7T 31 50 40 F Y Mab 1 7T/7T 19 *See Tables 1 and 2 for expansion of abbreviations. Login to comment 124 ABCC7 p.Arg117His ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Cys1344Ser ABCC7 p.Leu183Ile ABCC7 p.Phe650Leu The most phenotypically severe CFTR mutation, ⌬F508, was present in 12% of subjects in this study, compared to the general frequency of 3% in the white population in the United States.39,40 The R75Q mutation frequency was 14% in this study, compared to the general frequency of 1% in Northern Europeans.41 The intron 8 5T polymorphism was present in 17% of subjects in this study, compared to 5 to 10% in the general population.42,43 CFTR mutations identified in this study, including ⌬F508, R75Q, R117H, S1235R, D1152, L183I, and IVS8 5T, have been associated with mild symptoms of CF41,44-46 or with atypical manifestations of CF, such as isolated bronchiectasis14-17,19,20,22,23,25-27 and CBAVD.42,43,47 This study also reports three novel CFTR mutations, each in a separate patient with normal sweat chloride level: A394V, C1344S, and F650L. 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