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
X
ABCC7 p.Trp1098Cys 10798368:3:130
status: NEW
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ABCC7 p.Pro750Leu
X
ABCC7 p.Pro750Leu 10798368:3:138
status: NEW
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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
X
ABCC7 p.Trp1098Cys 10798368:14:438
status: NEW
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ABCC7 p.Pro750Leu
X
ABCC7 p.Pro750Leu 10798368:14:455
status: NEW
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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*
X
ABCC7 p.Gly542* 10798368:17:179
status: NEW
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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
X
ABCC7 p.Asn1303Lys 10798368:27:50
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 10798368:27:43
status: NEW
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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
X
ABCC7 p.Gly551Asp 10798368:28:7
status: NEW
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ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 10798368:28:0
status: NEW
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ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 10798368:28:21
status: NEW
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ABCC7 p.Ser549Asn
X
ABCC7 p.Ser549Asn 10798368:28:14
status: NEW
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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
X
ABCC7 p.Asn1303Lys 10798368:41:126
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 10798368:41:36
status: NEW
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ABCC7 p.Ser549Asn
X
ABCC7 p.Ser549Asn 10798368:41:107
status: NEW
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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
X
ABCC7 p.Gly551Asp 10798368:42:30
status: NEW
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ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 10798368:42:23
status: NEW
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ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 10798368:42:93
status: NEW
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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
X
ABCC7 p.Trp1098Cys 10798368:48:104
status: NEW
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ABCC7 p.Pro750Leu
X
ABCC7 p.Pro750Leu 10798368:48:115
status: NEW
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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
X
ABCC7 p.Trp1098Cys 10798368:49:5
status: NEW
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ABCC7 p.Trp1098Cys
X
ABCC7 p.Trp1098Cys 10798368:49:34
status: NEW
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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*
X
ABCC7 p.Arg75* 10798368:51:47
status: NEW
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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
X
ABCC7 p.Trp1098Cys 10798368:52:107
status: NEW
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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
X
ABCC7 p.Pro750Leu 10798368:53:0
status: NEW
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ABCC7 p.Pro750Leu
X
ABCC7 p.Pro750Leu 10798368:53:10
status: NEW
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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
X
ABCC7 p.Pro750Leu 10798368:56:38
status: NEW
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Because of the clinical findings, the P750L mutation was classified as severe. Login to comment
69 ABCC7 p.Gly551Asp
X
ABCC7 p.Gly551Asp 10798368:69:160
status: NEW
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ABCC7 p.Gly551Asp
X
ABCC7 p.Gly551Asp 10798368:69:553
status: NEW
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ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 10798368:69:638
status: NEW
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ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 10798368:69:170
status: NEW
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ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 10798368:69:566
status: NEW
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ABCC7 p.Gly551Ser
X
ABCC7 p.Gly551Ser 10798368:69:595
status: NEW
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ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 10798368:69:152
status: NEW
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ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 10798368:69:399
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 10798368:69:145
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 10798368:69:352
status: NEW
view ABCC7 p.Gly542* details
ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 10798368:69:893
status: NEW
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ABCC7 p.Val754Met
X
ABCC7 p.Val754Met 10798368:69:771
status: NEW
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ABCC7 p.Ile148Thr
X
ABCC7 p.Ile148Thr 10798368:69:448
status: NEW
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ABCC7 p.Gly85Glu
X
ABCC7 p.Gly85Glu 10798368:69:651
status: NEW
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ABCC7 p.Ser549Asn
X
ABCC7 p.Ser549Asn 10798368:69:386
status: NEW
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ABCC7 p.Arg75Gln
X
ABCC7 p.Arg75Gln 10798368:69:784
status: NEW
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ABCC7 p.Tyr1092*
X
ABCC7 p.Tyr1092* 10798368:69:624
status: NEW
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ABCC7 p.His199Tyr
X
ABCC7 p.His199Tyr 10798368:69:867
status: NEW
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ABCC7 p.Arg75*
X
ABCC7 p.Arg75* 10798368:69:413
status: NEW
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ABCC7 p.Trp1204*
X
ABCC7 p.Trp1204* 10798368:69:712
status: NEW
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ABCC7 p.Leu558Ser
X
ABCC7 p.Leu558Ser 10798368:69:810
status: NEW
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ABCC7 p.Ile506Thr
X
ABCC7 p.Ile506Thr 10798368:69:501
status: NEW
view ABCC7 p.Ile506Thr details
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*
X
ABCC7 p.Arg1162* 10798368:70:413
status: NEW
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ABCC7 p.Ser549Asn
X
ABCC7 p.Ser549Asn 10798368:70:201
status: NEW
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ABCC7 p.Trp1098Cys
X
ABCC7 p.Trp1098Cys 10798368:70:2
status: NEW
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ABCC7 p.Pro750Leu
X
ABCC7 p.Pro750Leu 10798368:70:24
status: NEW
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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*
X
ABCC7 p.Gly542* 10798368:74:4
status: NEW
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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
X
ABCC7 p.Ser549Asn 10798368:77:26
status: NEW
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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
X
ABCC7 p.Gly551Asp 10798368:78:17
status: NEW
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ABCC7 p.Arg553*
X
ABCC7 p.Arg553* 10798368:78:27
status: NEW
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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
X
ABCC7 p.Gly551Asp 10798368:79:24
status: NEW
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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
X
ABCC7 p.Trp1098Cys 10798368:88:0
status: NEW
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ABCC7 p.Arg75*
X
ABCC7 p.Arg75* 10798368:88:108
status: NEW
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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