ABCMdb

PMID: 12437773

Huber K, Mirkovic B, Nersesian R, Myers A, Saiki R, Bauer K
Survey of CF mutations in the clinical laboratory.
BMC Clin Pathol. 2002 Nov 19;2(1):4., 2002-11-19 [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Gly542* The only other CF-alleles that we found with these tests were the G542X allele (3 persons), the G551D allele (3 persons), the 3849+10kb C-T allele (2 persons) the R117H allele (2 persons) and the 621+1G-T allele (1 person). Login to comment 35 ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro All probands (or their par- Table 1: Exons and introns that are amplified with the line probe assay, and the mutations they encompass Roche assay: Amplicon Mutations exon 4 R117H,621+1G → T exon 7 R334W, R347P exon 9 A455E, 5/7/9T polymorphism exon 10 ∆1507, ∆F508. Login to comment 36 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.Arg1162* ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr ABCC7 p.Phe508Cys ABCC7 p.Ile506Val ABCC7 p.Glu60* ABCC7 p.Ile507Val F508C, I507V, I506V polymorphism exon 11 1717-1G → A, G542X, S549N, G551D, R553X, R560T exon 20 W1282X exon 21 N1303K intron 19 3849+10kb C → T Innogenetics assay: exon 3 394delTT, G85E, E60X exon/intron 4 621+1G-T, R117H exon 7 1078delT, R347P, R334W exon 13 2143delT, 2183AA-G, 2184delA exon 19 R1162X, 3659delC intron 5 711+5G-A intron8/exon 9 A455E,, 5T,7T,9T intron 14b 2789+5G-A intron 19 3849+10kb C-T Table 2: Genotypes of patients with mutations, final results Group 1) (patients with symptoms typical for/indicative of CF) No. Login to comment 38 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Gly542* ABCC7 p.Gly542* IRT, normal sweat test f 0 7T/9T DF508/3849+10kb C-T x 2 CF, substantiation f 0 9T/9T 621+1G-T/621+1G-T 3 CF, substantiation f 1 9T/9T DF508/DF508 x 4 CF, substantiation f 5 9T/9T DF508/DF508 x x x 5 CF, substantiation f 7 9T/9T DF508/G542X x x 6 CF, substantiation, rec. diarrhoe, pancreas insufficiency, pos. sweat test f 8 9T/9T DF508/DF508 x 7 CF, substantiation f 12 9T/9T DF508/DF508 x 8 CF, substantiation f 13 9T/9T DF508/DF508 x 9 f 13 7T/9T DF508/WT 10 CF, substantiation f 16 9T/9T DF508/G542X 11 indicative linkage analysis f 22 7T/9T DF508/WT x 12 f 24 7T/9T DF508/WT x 13 bronchiectasis, bronchopulmonal infections since infancy f 28 7T/9T DF508/3849+10kbC-T x 14 pos. sweat test f 28 9T/9T DF508/WT x 15 typical clinic, pos. sweat test f 31 7T/9T DF508/WT x x 16 f 32 7T/7T 3849+10kb C-T/WT 17 pulmonal course typical of CF f 32 7T/9T DF508/WT x x x 18 f 34 7T/7T G551D/WT x x 19 f 41 7T/7T DF508/WT 20 CF, substantiation f 56 7T/9T DF508/3849+10kb C-T x 21 22 CF, substantiation m 0 9T/9T DF508/DF508 x 23 m 1 7T/9T DF508/WT x 24 impaired lung function, intestinal complications m 3 7T/9T DF508/WT x x 25 CF, substantiation m 5 9T/9T DF508/DF508 26 m 12 7T/7T G551D/WT x x 27 CF, substantiation m 17 9T/9T DF508/DF508 28 m 18 7T/7T R117H/WT&1466delAATT/1466delAATT 1466delAATT x 29 pos sweat test m 20 7T/9T DF508/WT 30 CF, substantiation m 25 9T/9T DF508/DF508 31 . Login to comment 40 ABCC7 p.Arg117His ABCC7 p.Gly542* infect., azoospermia, pancreatitis m 31 9T/9T DF508/WT 35 CF, substantiation m 33 9T/9T DF508/DF508 x 36 m 33 7T/9T DF508/WT 37 m 33 7T/9T DF508/WT 38 m 38 7T/9T R117H/G542X Group 2a) (Patients from IVF clinics) No. Login to comment 41 ABCC7 p.Gly542* : Diagnosis Sex Age Intron 8 16 mut. 29 mut.b seq.c DGGEd 39 m 24 7T/9T WT 40 m 25 9T/9T WT 41 m 28 5T/9T DF508/WT x 42 m 28 5T/9T DF508/WT 43 m 29 5T/9T DF508/WT x x x 44 m 30 7T/7T WT x 45 m 31 5T/9T DF508/WT x x x 46 m 31 7T/7T WT x 47 m 31 7T/9T WT x 48 m 33 7T/9T DF508/WT x 49 m 34 7T/7T WT x 50 m 34 9T/9T DF508/WT x 51 m 35 7T/9T G542X/WT 52 m 36 5T/9T DF508/WT ents, respectively) had given informed consent for genetic analysis as required by the Austrian law. Login to comment 50 ABCC7 p.Gly551Asp ABCC7 p.Gly542* : Diagnosis Sex Age Intron 8 16 mut. 29 mut.b seq.c DGGEd 59 f 42 7T/7T 3849+10kb C-T/WT x 60 f 15 7T/9T DF508/WT x 61 f 20 7T/9T DF508/WT x 62 f 23 7T/9T DF508/WT x 63 f 25 7T/9T DF508/WT x x x 64 f 26 7T/9T DF508/WT 65 f 32 7T/9T DF508/WT x 66 f 40 7T/9T DF508/WT x x 67 f 65 9T/9T DF508/WT 68 f 30 7T/9T DF508/WT x 69 m 14 9T/9T DF508/WT x 70 m 16 7T/9T DF508/WT 71 m 25 7T/9T DF508/WT x x x 72 m 28 5T/9T DF508/WT x 73 m 32 7T/9T DF508/WT x x 74 m 45 7T/9T DF508/WT x x 75 m 48 7T/9T DF508/WT x 76 m 69 7T/9T DF508/WT 77 m 30 7T/9T G542X/WT x x 78 m 15 7T/7T G551D/WT x Details for diagnoses, number of mutations analysed, methods used, and other specifics for individuals with found mutations within the three groups are shown. Login to comment 95 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Gly542* Among 114 children < 18 yrs in group 1), we found 9 patients to be homozygote for ∆F508, two compound heterozygote for ∆F508/G542X, one compound heterozygote for ∆F508/3849+10kbC-T, five heterozygote for ∆F508, one G551D/WT, one R117H/WT, one homozygote for 621+1G-T, and one girl with 5T/7T alleles in intron 8 (total of 18% with mutations). Login to comment 96 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Gly542* Twenty-two percent of the adults in group 1) had CFTR mutations, namely two ∆F508/∆F508, thirteen ∆F508/ WT, one compound for R117H/WT and 1466delAATT (frameshift mutation in exon 9), one R117H/G542X, one G551D/WT, one 3849+10kb C-T/WT, one compound heterozygote for ∆F508/1248+1 A → G (splice mutation in intron 7), and two individuals with ∆F508/3849+10kb C-T. Login to comment 102 ABCC7 p.Gly542* Nine of these men (45%) had normal alleles (and a benign thymidine polymorphism in intron 8) at the loci analysed, seven men had a genotype of 5T/9T with ∆F508/WT, one showed 7T/9T with ∆F508/ WT, one had 9T/9T with ∆F508/WT, and one had 7T/9T with G542X/WT. Login to comment 106 ABCC7 p.Gly551Asp ABCC7 p.Gly542* Of 54 individuals in group 3, tested because their partners or relatives had CFTR mutations, 37% had mutated alleles: seventeen persons had the genotype ∆F508/WT, one had G551D/WT, one had 3849+10kb C-T, and one person had G542X/WT (table 2). Login to comment 116 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Gly542* In comparison to CF mutation-frequencies in some European countries, the CF alleles we found (>2%) with our tests show the following distribution in our cohort: ∆F508: 83% (Romania:27%, Switzerland: 43%, Denmark: 87,2% [19]); G542X: 4,4% (France: 3,1%, Italy: 4,8%, Spain: 7,7%); G551D: 4,4% (UK: 3,1%, Czechia: 4,0%, Ireland: 6,9%), 3849+10kbC-T: 2,9% (Germany: 1,2%, Poland: 2,6%, Latvia: 12,5%), R117H: 2,9% (Greece: 1,2%, Ireland: 2,0%, Norway: 3,0%) Because we participate in the European Quality assessment trial for Cystic Fibrosis, we could evaluate the quality of the Roche Amplicor CF test in this regard as well. Login to comment 117 ABCC7 p.Gly551Asp ABCC7 p.Arg553* In the case of the G551D/WT R553X/WT genotype, the Roche test needs careful interpretation (and ought to be improved) because the hybridisation at the one locus destabilised the hybridisation at the other locus which is only 4 bp apart. Login to comment 118 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553* Accordingly, the line assay showed a G551D/G551D and R553X/R553X (two homozygote mutations) genotype instead of the correct G551D/WT and R553X/WT (compound heterozygote) genotype. Login to comment