ABCMdb

PMID: 12706377

Streit C, Burlamaque-Neto AC, de Abreu e Silva F, Giugliani R, Saraiva Pereira ML
CFTR gene: molecular analysis in patients from South Brazil.
Mol Genet Metab. 2003 Apr;78(4):259-64., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Gln359Lys The present work aimed (1) to detect sequence alterations in the nucleotide binding regions and at the membrane spanning domain of the CFTR gene and (2) to detect the following frequent mutations R347P, R347H, R334W, and Q359K (located in exon 7), DF508 (located in exon 10), G542X, G551D, R553X, and S549N (located in exon 11), W1282X (located in exon 20), and N1303K (located in exon 21). Login to comment 7 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Gly542* Frequencies of G542X, R334W, R553X, and W1282X mutations in our population were 3.25, 1.3, 0.65, and 0.65%, respectively. Login to comment 8 ABCC7 p.Gly551Asp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Ser549Asn ABCC7 p.Gln359Lys No alleles were found to carry mutations G551D, R334W, R347P, R347H, Q359K, S549N, and N1303K, which were included in the screening protocol. Login to comment 30 ABCC7 p.Trp1282* doi:10.1016/S1096-7192(03)00033-7 Four other mutant alleles for CF occur at a relative frequency greater than 1%; however, some mutations are unusually common in specific populations, such as W1282X among Ashkenazi Jews [3]. Login to comment 34 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gln359Lys The main aims of the present work were (1) to establish the frequency of the DF508 mutation this studied population, (2) to identify alterations in the nucleotide sequence of the exons 3, 5, and 7 which are located in the first membrane spanning domain (MSD1); of exons 9, 10, 11, and 12 which are located in the first nucleotide binding domain (NBD1); of exons 19, 20, 21, and 22 which are located in the second nucleotide binding domain (NBD2) of the CFTR gene, and finally (3) to identify some specific frequent mutations (R347P, R347H, R334W, Q359K, G542X, G551D, R553X, S54 9N, W1282X, and N1303K) in these patients. Login to comment 59 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Gln359Lys Restriction fragment length polymorphism Mutations R347P, R347H, R334W, Q359K (located in exon 7), G542X, S549N, G551D, R553X mutations (exon 11), W1282X (exon 20), and N1303K (exon 21) were identified by restriction fragment length polymorphism (RFLP) protocol, using specific restriction endonucleases. Login to comment 60 ABCC7 p.Gly551Asp ABCC7 p.Arg553* G551D and R553X mutations were detected by a combined RFLP using HincII and MboI as described previously [18,19]. Login to comment 61 ABCC7 p.Gly542* RFLP using BstNI was used to detect the G542X mutation, because this alteration destroys the recognition site for this enzyme. Login to comment 62 ABCC7 p.Asn1303Lys The amplification created restriction site (ACRS) was used to identify the N1303K mutation as previously described by Haliassos et al. [20]. Login to comment 63 ABCC7 p.Asn1303Lys Using a modified primer on the 30 side of codon 1303, the N1303K mutation could be detected as a loss of a BstNI recognition site [21]. Login to comment 64 ABCC7 p.Trp1282* W1282X mutation was also detected by RFLP. Login to comment 65 ABCC7 p.Trp1282* PCR product of exon 20 has two MnlI sites, one of which is destroyed by the W1282X mutation [22]. Login to comment 66 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Gly542* Positive controls were used along with samples to be tested for G542X, G551D, and R553X mutations during the experiments. Login to comment 76 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Gln359Lys Screening of four additional mutations (G542X, R553X, R334W, and W1282X) together with DF508 Table 2 Mutations detected in 77 CF patients from south region of Brazil Mutation Location Number of alleles Frequency (%) R334W Exon 7 2 1.3 R347P Exon 7 0 0 R347H Exon 7 0 0 Q359K Exon 7 0 0 DF508 Exon 10 75 48.7 S549N Exon 11 0 0 G542X Exon 11 5 3.2 G551D Exon 11 0 0 R553X Exon 11 1 0.7 W1282X Exon 20 1 0.7 N1303K Exon 21 0 0 ? Login to comment 83 ABCC7 p.Gly542* ABCC7 p.Gly542* Three patients (3.9%) carry the G542X mutation in only one allele and an unknown mutation in the other (G542X/?). Login to comment 84 ABCC7 p.Gly542* ABCC7 p.Gly542* Two patients (2.6%) were a compound heterozygote for the DF508 and the G542X mutation (DF508/G542X). Login to comment 85 ABCC7 p.Arg553* ABCC7 p.Arg553* One patient (1.3%) was a compound heterozygous compound for DF508 and R553X mutation (DF508/R553X). Login to comment 86 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp One patient (1.3%) was a compound heterozygote for DF508 and R334W mutations (DF508/R334W). Login to comment 87 ABCC7 p.Trp1282* ABCC7 p.Trp1282* One patient (1.3%) was a compound heterozygote for DF508 and W1282X mutations (DF508/W1282X). Login to comment 88 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp One patient (1.3%) had in one allele the R334W mutation and in other allele an undetected mutation (R334W/?). Login to comment 101 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* On the other hand, estimated frequencies of G542X, N1303K, and W1282X mutations among alleles of affected patients in our population were 8.35, 1.6, and 0.8%, respectively [26]. Login to comment 102 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Gly542* Frequencies of DF508, G542X, G551D, and R553X mutations in our study were similar to that established for South Europe [27]. Login to comment 111 ABCC7 p.Arg553* ABCC7 p.Gly542* The G542X and R553X mutations showed frequencies similar to those observed in south European countries (http://www.genet.sickids.on.ca) [25]. Login to comment 112 ABCC7 p.Gly551Asp ABCC7 p.Asn1303Lys In the present study, the G551D and N1303K mutations were investigated but no alleles with these mutations were found, suggesting that they are not very common in this part of Brazil. Login to comment 113 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Gly542* DNA screening for four common CF mutations (G542X, R553X, R334W, and W1282X), together with DF508, enabled the detection of 84 out of the 154 CF alleles in our sample, that represents 54.5% of studied alleles. Login to comment