ABCMdb

PMID: 10798368

Orozco L, Velazquez R, Zielenski J, Tsui LC, Chavez M, Lezana JL, Saldana Y, Hernandez E, Carnevale A
Spectrum of CFTR mutations in Mexican cystic fibrosis patients: identification of five novel mutations (W1098C, 846delT, P750L, 4160insGGGG and 297-1G-->A).
Hum Genet. 2000 Mar;106(3):360-5., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCC7 p.Trp1098Cys ABCC7 p.Pro750Leu A total of 34 different mutations representing 74.58% of the CF chromosomes were identified, including five novel CFTR mutations: W1098C, P750L, 846delT, 4160insGGGG and 297-1G→A. Login to comment 14 ABCC7 p.Trp1098Cys ABCC7 p.Pro750Leu Mexican Indian ancestry is also very different from other Latin American populations such as in Ar- Lorena Orozco · Rafael Velázquez · Julian Zielenski · Lap-Chee Tsui · Margarita Chávez · José Luis Lezana · Yolanda Saldaña · Elizabeth Hernández · Alessandra Carnevale Spectrum of CFTR mutations in Mexican cystic fibrosis patients: identification of five novel mutations (W1098C, 846delT, P750L, 4160insGGGG and 297-1G→A) Hum Genet (2000) 106:360-365 Digital Object Identifier (DOI) 10.1007/s004390000244 Received: 26 October 1999 / Accepted: 11 January 2000 / Published online: 11 February 2000 ORIGINAL INVESTIGATION L. Orozco1 (u) · R. Velázquez · M. Chávez · Y. Saldaña · E. Hernández · A. Carnevale Molecular Biology Laboratory, Department of Research in Human Genetics, National Institute of Pediatrics, Mexico City, Mexico L. Orozco · R. Velázquez · Y. Saldaña Interinstitutional Program of Molecular Biomedicine, CICATA-IPN, Mexico City, Mexico J. Zielenski · L.-C. Tsui Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada J.L. Lezana Asociación Mexicana de Fibrosis Quística, Mexico City, Mexico Contact address: 1 Laboratorio de Biología Molecular, Instituto Nacional de Pediatría, Insurgentes Sur No. 3700-C, Col. Insurgentes-Cuicuilco, Del. Login to comment 17 ABCC7 p.Gly542* We previously reported that only 39% of CF chromosomes from Mexican patients with Mestee ethnic background carry the ∆F508 mutation (Orozco et al. 1993) and 7.2% carry the G542X mutation (Villarreal et al. 1996), which is common in the Spanish population (Casals et al. 1997). Login to comment 27 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Detection of known mutations ∆F508, G542X, N1303K, ∆I507 and 2869insG were screened by PCR-mediated site directed mutagenesis (PSM) as previously described (Friedman et al. 1991). Login to comment 28 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Arg1162* ABCC7 p.Ser549Asn R553X, G551D, S549N, R1162X, and 3120+1G→A were tested by PCR-based restriction analysis as previously described (Osborne et al. 1992; Jones et al. 1992; Picci et al. 1992; Shoshani et al. 1992). Login to comment 41 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn The second most common mutation was G542X, present in 6.1% of CF chromosomes, followed by ∆I507 and S549N (each 2.5%), N1303K (2.06%) and 2055del→A (1.03%). Login to comment 42 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Arg1162* On the other hand, the R553X, G551D and 1924del7 mutations had a frequency <1% and 2869insG, R1162X, 3120+1G→A were not found in the population studied. Login to comment 48 ABCC7 p.Trp1098Cys ABCC7 p.Pro750Leu Novel mutations At present, we have identified a total of five novel mutations: two missense mutations (W1098C and P750L), two frameshift mutations (846delT and 4160insGGGG) and one splice site mutation (297-1G→A). Login to comment 49 ABCC7 p.Trp1098Cys ABCC7 p.Trp1098Cys 361 W1098C The missense mutation W1098C was caused by transversion of G to T detected at nucleotide position 3426 in exon 17b of the CFTR gene on the maternal chromosome. Login to comment 51 ABCC7 p.Arg75* It was found in a male patient who carries the R75X severe mutation on exon 3 of the paternal allele. Login to comment 52 ABCC7 p.Trp1098Cys The patient was diagnosed with the disease at 23 years of age with pancreatic sufficiency, suggesting that W1098C is a mild mutation. Login to comment 53 ABCC7 p.Pro750Leu ABCC7 p.Pro750Leu P750L The P750L mutation was caused by the transition of C to T at nucleotide position 2381 in exon 13b. Login to comment 56 ABCC7 p.Pro750Leu Because of the clinical findings, the P750L mutation was classified as severe. Login to comment 69 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Gly551Ser ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Val754Met ABCC7 p.Ile148Thr ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Arg75Gln ABCC7 p.Tyr1092* ABCC7 p.His199Tyr ABCC7 p.Arg75* ABCC7 p.Trp1204* ABCC7 p.Leu558Ser ABCC7 p.Ile506Thr First, we tested these patients for 12 mutations selected for the following reasons: five are the most common mutations worldwide (∆F508, G542X, N1303K, G551D and R553X; CFGAC 1994); 362 Table 1 Frequency of the CFTR gene mutations in 97 (194 chromosomes) Mexican patients Mutation Number of Frequency affected alleles (%) ∆F508 79 40.72 G542X 12 6.18 ∆I507 5 2.57 S549N 5 2.57 N1303K 4 2.06 R75X 3 1.54 406-1G→A 3 1.54 I148T 3 1.54 2055del9→A 2 1.03 935delA 2 1.03 I506T 2 1.03 3199del6 2 1.03 2183AA→G 2 1.03 G551D 1 0.51 R553X 1 0.51 1924del7 1 0.51 G551S 1 0.51 1078delT 1 0.51 Y1092X 1 0.51 R117H 1 0.51 G85E 1 0.51 3849+10KbC→T 1 0.51 1716G→A 1 0.51 W1204X 1 0.51 W1098Ca 1 0.51 846delTa 1 0.51 P750La 1 0.51 V754M 1 0.51 R75Q 1 0.51 W1069X 1 0.51 L558S 1 0.51 4160insGGGGa 1 0.51 297-1G→Aa 1 0.51 H199Y 1 0.51 2869insG 0 0 R1162X 0 0 3120+1G→A 0 0 Total 34 145 74.58% aNovel mutations detected in this study Fig.1 Sequencing ladders showing the CFTR novel mutations. Login to comment 70 ABCC7 p.Arg1162* ABCC7 p.Ser549Asn ABCC7 p.Trp1098Cys ABCC7 p.Pro750Leu a W1098C (antisense), b P750L (antisense), c 846delT (antisense), d 4160insGGGG (antisense), e 297-1GA (antisense) three mutations were found in our population during a preliminary screening by SSCP (S549N, 2055del9→A and 1924del7; Orozco et al. 1997); ∆I507 was found during the screening for ∆F508 (Orozco et al. 1994); and three mutations described at least once in Hispanic populations (R1162X, 2869insG; Casals et al. 1997; 3120+ 1G→A; CFGAC 1994). Login to comment 74 ABCC7 p.Gly542* The G542X mutation has a frequency higher (6.1%) than that reported to the CFGAC, but similar to Spanish patients (Casals et al. 1997). Login to comment 77 ABCC7 p.Ser549Asn It is noteworthy that the S549N mutation was relatively frequent in our patients (2.5%) whereas its worldwide frequency is below 0.1%, and it was absent in a sample of 640 Spanish CF families (Casals et al. 1997), and in 114 Argentinean families (Chertkoff et al. 1997). Login to comment 78 ABCC7 p.Gly551Asp ABCC7 p.Arg553* In contrast, the G551D and R553X mutations, which are among the first five most common worldwide, were only found in one chromosome each. Login to comment 79 ABCC7 p.Gly551Asp In particular, mutation G551D has a high frequency in northern European and USA populations, while it is very rare in Hispanic and Latin American CF patients (CFGAC 1994). Login to comment 88 ABCC7 p.Trp1098Cys ABCC7 p.Arg75* W1098C seems to be a mild mutation because the phenotype is mild despite the presence of a severe mutation (R75X) on the other chromosome. Login to comment