ABCMdb

PMID: 8947061

Hubert D, Bienvenu T, Desmazes-Dufeu N, Fajac I, Lacronique J, Matran R, Kaplan JC, Dusser DJ
Genotype-phenotype relationships in a cohort of adult cystic fibrosis patients.
Eur Respir J. 1996 Nov;9(11):2207-14., [PubMed]

Sentences

No. Mutations Sentence Comment

22 ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu ABCC7 p.Gly551Ser ABCC7 p.Gly551Ser Concerning the relationship between the severity of pulmonary involvement and other mutations than ∆F508, a mild pulmonary disease was described in two sisters homozygous for the G551S mutation [13], and in compound heterozygotes for the missense mutation A455E, a mutation commonly found in The Netherlands [14]. Login to comment 32 ABCC7 p.Gly542* ABCC7 p.Arg1070Gln ABCC7 p.Arg1070Gln ABCC7 p.Asp1152His ABCC7 p.Asp1152His Only three patients had a normal sweat test: two related patients, who were compound heterozygotes for the G542X and 3849+10 kb cytosine (C)→thymine (T) mutations, and one patient who was compound heterozygote for the R1070Q and D1152H mutations. Login to comment 65 ABCC7 p.Gly542* ABCC7 p.Gly542* The ∆F508 mutation was found in 134 chromosomes (61%), the mutation G542X in nine (4%), whereas all the other mutations were rare, since they were found in no more than 1% of the cohort. Login to comment 77 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Ser1251Asn ABCC7 p.Ser1251Asn ABCC7 p.Pro205Ser ABCC7 p.Pro205Ser ABCC7 p.Arg1070Gln ABCC7 p.Arg1070Gln ABCC7 p.Arg1070Gln ABCC7 p.Arg1070Gln ABCC7 p.Asn1303His ABCC7 p.Asn1303His ABCC7 p.Tyr1092* ABCC7 p.Tyr1092* ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Gly27Glu ABCC7 p.Gly27Glu ABCC7 p.Trp846* ABCC7 p.Trp846* ABCC7 p.Ile336Lys ABCC7 p.Ile336Lys ABCC7 p.Glu60* ABCC7 p.Glu60* ABCC7 p.Ile980Lys ABCC7 p.Ile980Lys ABCC7 p.Glu827* ABCC7 p.Glu827* ABCC7 p.Trp361Arg ABCC7 p.Trp361Arg ABCC7 p.Asp192Asn ABCC7 p.Asp192Asn - Genotype of the 110 CF patients: details of the CF mutations and classification into four groups Genotype Genotype Pts groups n 1 ∆F508/∆F508 48* 2 ∆F508/G542X 6 ∆F508/E827X 3† ∆;F508/R553X 2 Ƞ6;F508/W1282X 2 ∆F508/E595X 1 206;F508/E60X 1 ∆F508/W846X 1 ∆F508/1078delT 1 ∆F508/2143delT 1 ∆F508/2347delG 1 ∆F508/3659delC 1 ∆F508/4382delA 1 ∆F508/2183 AA→G 1 ∆F508/1717-1 G→A 1 ∆F508/1811+1.6 kb A→G 1 E595X/Y1092X 1 1717-1 G→A/1078delT 1 3 ∆F508/I336K 1 ∆F508/G27E 1 ∆F508/D192N 1 ∆F508//I980K 1 ∆F508/P205S 1 ∆F508/2789+5 G→A 1 ∆F508/3272-26 A→G 1 G542X/3849+10 kb C→T 2‡ G542X/2789+5 G→A 1 W361R/297-3 C→T 1 G551D/1717-1 G→A 1 N1303H/2183 AA→G 1 2789+5 G→A/2183 AA→G 1 R1070Q/D1152H 1 R1070Q/unidentified 1 S1251N/unidentified 1 4 ∆F508/unidentified 7 ∆I507/unidentified 2 1811+1.6 kb A→G/unidentified 1 1161delC/unidentified 1 unidentified/unidentified 8 *: two patients are brothers; †: three brothers; ‡: two sisters. Login to comment 105 ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Trp361Arg ABCC7 p.Trp361Arg - Characteristics of patients with pancreatic sufficiency and FEV1 <30% of predicted value Age at P. aeruginosa Genotype Age diagnosis FVC FEV1 colonization yrs yrs % pred % pred Group 2 ∆F508/4382del A 27 18 43 21 Yes Group 3 ∆F508/3272-26 G→A 21 8 32 28 Yes G542X/3849+10kb C→T 35 32 53 25 Yes W361R/297-3 C→T 45 25 25 12 Yes Group 4 unid/unid 30 15 38 27 Yes unid: unidentified. For further definitions see legends to tables 1 and 3. Login to comment 107 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly27Glu ABCC7 p.Gly27Glu ABCC7 p.Trp846* ABCC7 p.Trp846* ABCC7 p.Glu827* ABCC7 p.Glu827* - Characteristics of patients with FEV1 >70% of predicted value Age at P. aeruginosa PI Hepatic Genotype Age diagnosis FVC FEV1 colonization cirrhosis yrs yrs % pred % pred Group 1 ∆F508/∆F508 18 <1 83 75 Yes Yes No ∆F508/∆F508 19 8 88 72 Yes Yes Yes ∆F508/∆F508 24 <1 87 84 Yes Yes No ∆F508/∆F508 25 13 85 82 Yes Yes No ∆F508/∆F508 37 34 90 83 No Yes No Group 2 ∆F508/E827X 18 <1 82 76 Yes Yes Yes ∆F508/W846X 29 27 101 95 No Yes No Ƞ6;F508/W1282X 31 28 91 77 No Yes No Group 3 2789+5 G→A/G542X 18 2 107 103 No No No 2789+5 G→A/2183 AA→G 36 34 93 87 No No No ∆F508/G27E 39 28 115 78 No No No Group 4 ∆I507/unid 18 <1 103 103 No Yes No unid/unid 26 5 89 77 No Yes No unid/unid 39 38 96 87 No No No unid/unid 40 38 110 106 No No No PI: pancreatic insufficiency; unid: unidentified. For further definitions see legend to tables 1 and 3. and the nature of pulmonary infection are very different among patients. Login to comment 112 ABCC7 p.Ala455Glu ABCC7 p.Gly551Ser In the studies by GAN et al. [14], and STRONG et al. [13] patients with the A455E mutation or with the G551S mutation, respectively, who would be classified as Group 3 in the present study, had mild pulmonary disease. Login to comment 116 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Gly542* In the latter study, most of the compound heterozygotes for ∆F508 were associated with another mutation (G542X, R553X, W1282X, 1717- 1G→A, 621+1G→T) that corresponded to Group 2. Login to comment 118 ABCC7 p.Arg117His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys For the two genotypes, R117H/∆F508 and N1303K/∆F508, which would be classified as Group 3, the lack of difference in pulmonary involvement might be due to a selection bias created by mortality in this cross-sectional study and/or by the young age of the patients in most groups of this study, since the mean age of all groups but one was less than 15 yrs. Login to comment 136 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp846* ABCC7 p.Trp846* ABCC7 p.Glu827* ABCC7 p.Glu827* These cases were mostly observed in Groups 1 and 2, despite a ∆F508 mutation either homozygote or associated with a nonsense mutation (E827X, W846X and W1282X). Login to comment