ABCMdb

PMID: 10794365

Bernardino AL, Ferri A, Passos-Bueno MR, Kim CE, Nakaie CM, Gomes CE, Damaceno N, Zatz M
Molecular analysis in Brazilian cystic fibrosis patients reveals five novel mutations.
Genet Test. 2000;4(1):69-74., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp ABCC7 p.Val232Asp ABCC7 p.Arg851Leu ABCC7 p.Trp1089* Another fifteen mutations (previously reported) were detected: G542X, R1162X, N1303K, R334W, W1282X, G58E, L206W, R553X, 6211 1GRT, V232D, 1717-1GRA, 2347 delG, R851L, 27891 5GRA, and W1089X. Login to comment 7 ABCC7 p.Val201Met ABCC7 p.Tyr275* Five novel mutations were identified, V201M (exon 6a), Y275X (exon 6b), 2686 insT (exon 14a), 3171 delC (exon 17a), and 3617 delGA (exon 19). Login to comment 9 ABCC7 p.Tyr275* In addition, the identification of the novel mutation Y275X allowed prenatal diagnosis in a high-risk fetus. Login to comment 51 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp The next most common mutations were: G542X (8.8%), R1162X (2.5%), N1303K (2.5%), R334W (2.5%), W1282X (1.3%), G58E (1.3%), L206W (0.6%), and R553X (0.6%). Login to comment 53 ABCC7 p.Val232Asp ABCC7 p.Arg851Leu ABCC7 p.Trp1089* Seven other rare mutations were also identified : 6211 1GRT (exon 4), V232D (exon 6a), 1717-1G RA (intron 11), 2347 delG (exon 13b), R851L (exon 14a), 27891 5GRA (intron 14b), and W1089X (exon 17b). Login to comment 66 ABCC7 p.Tyr275* Y275X: This GRC transition was detected at position 957 in exon 6b, resulting in the replacement of a tyrosine (position 275) by a termination codon. Login to comment 69 ABCC7 p.Val201Met V201M: This GRA transition, at position 733 in exon 6a, leads to the substitution of a valine for a methionine. Login to comment 81 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp ABCC7 p.Val232Asp ABCC7 p.Arg851Leu ABCC7 p.Trp1089* In this study, 16 mutations were identified: D F508, G542X, R1162X, N1303K, R334W, W1282X, G58E, L206W, R553X, 6211 1GRT, V232D, 1717-1GRA, 2347 delG, R851L, 27891 5GRA, and W1089X. Login to comment 84 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Val232Asp ABCC7 p.Arg851Leu ABCC7 p.Trp1089* ABCC7 p.Val201Met ABCC7 p.Tyr275* GEN OTYPES, FREQUENCIES, AN D PRESENCE OF PI FRO M 160 CF PATIE NTS (320 CF CHROM OSOM ES) Number and frequency (%) Genotype Number Frequency (%) of patients with PI D F508/D F508 47 29.40 47 (100%) D F508/G542X 13 8.10 13 (100%) D F508/R1162X 6 3.80 6 (100%) D F508/R334W 5 3.10 3 (60%) D F508/N1303K 3 1.90 3 (100%) D F508/W1282X 2 1.20 2 (100%) D F508/G58E 2 1.20 1 (50%) D F508/L206W 1 0.62 0 D F508/R553X 1 0.62 1 (100%) D F508/R851L 1 0.62 0 D F508/2789 1 5g ® A 1 0.62 0 D F508/3617delGA 1 0.62 1 (100%) D F508/3171delC 1 0.62 1 (100%) D F508/2686insT 1 0.62 1 (100%) D F508/Y275X 1 0.62 1 (100%) D F508/U 22 13.80 14 (64%) G542X/G542X 3 1.90 3 (100%) G542X/N1303K 3 1.90 2 (67%) G542X/R1162X 1 0.62 1 (100%) G542X/U 5 3.10 4 (80%) N1303K/R1162X 1 0.62 1 (100%) N1303K/G58E 1 0.62 0 2347delG/2347delG 1 0.62 1 (100%) R334W/V232D 1 0.62 0 R334W/W1089X 1 0.62 1 (100%) R334W/U 1 0.62 1 (100%) W1282X/U 1 0.62 1 (100%) G58E/U 1 0.62 1 (100%) R553X/U 1 0.62 1 (100%) L206W/U 1 0.62 0 621 1 1G ® T/U 1 0.62 1 (100%) 1717-1G ® A/U 1 0.62 Not known V201M/U 1 0.62 0 U/U 27 16.90 12 (44%) Total 160 100 - U, Unknown CF mutation. Login to comment 88 ABCC7 p.Gly542* The second most common mutation, G542X, which occurred in 8.8% of our patients, is also the second most frequently reported in Spanish Mediterranean coastal areas (8.0%) (Casals et al., 1993). Login to comment 89 ABCC7 p.Asn1303Lys ABCC7 p.Arg1162* Two other mutations-N1303K (2.5%) and R1162X (2.5%)-were also found in frequencies compatible with the ethnic origins of our Caucasian population. Login to comment 90 ABCC7 p.Asn1303Lys ABCC7 p.Arg1162* The N1303K mutation has been reported in Southern Europeans as the fourth most common mutation, with a frequency of 3.2% (Nunes et al., 1991), and the R1162X mutation is the second most frequent mutation in Northern Italy (about 10%) (Casals et al., 1993). Login to comment 91 ABCC7 p.Arg334Trp However, the R334W mutation, which we found in 8 patients, is apparently more frequent in our population (2.5%) than the 0.4% frequency reported worldwide (Tsui, 1992). Login to comment 104 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* However, one of our compound heterozygote patients for severe mutations (N1303K/G542X), has PS. Login to comment 105 ABCC7 p.Arg334Trp The mutation R334W, which is considered a later-onset PI mutation, was first reported to be associated with PS (Kristidis et al., 1992). Login to comment 107 ABCC7 p.Arg334Trp The proportion of PI patients with the R334W mutation in our sample (63%), is similar to the values found by Estivill et al. (1995). Login to comment 110 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Unexpectedly, however one compound heterozygote (N1303K/G542X) CF patients (who was referred to above as having PS) was the son of first cousins, which is compatible with the high frequency of CFTR heterozygotes in the population. Login to comment 113 ABCC7 p.Val201Met The fifth mutation, the V201M change, is a missense mutation; however, it is probably the cause of disease in the affected individual, because it was not found in 200 normal chromosomes. Login to comment 116 ABCC7 p.Tyr275* One of them, the Y275X mutation (Fig. 1), is probably of Indian origin and was particularly important because it allowed a prenatal diagnosis in a high-risk fetus. Login to comment 118 ABCC7 p.Tyr275* Mutation Y275X. Login to comment 125 ABCC7 p.Tyr275* However, the Y275X mutation identified in the father was not found in the fetus. Login to comment