ABCMdb

PMID: 16963320

Perez MM, Luna MC, Pivetta OH, Keyeux G
CFTR gene analysis in Latin American CF patients: heterogeneous origin and distribution of mutations across the continent.
J Cyst Fibros. 2007 May;6(3):194-208. Epub 2006 Sep 11., [PubMed]

Sentences

No. Mutations Sentence Comment

42 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly551Ser ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Val754Met ABCC7 p.Leu206Trp ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Arg1066Cys ABCC7 p.Gln220* ABCC7 p.Tyr1092* ABCC7 p.His199Tyr ABCC7 p.Arg1283Met ABCC7 p.Ile1027Thr ABCC7 p.Val232Asp ABCC7 p.Arg851Leu ABCC7 p.Trp1089* ABCC7 p.Val201Met ABCC7 p.Pro750Leu ABCC7 p.Arg75* ABCC7 p.Trp1204* ABCC7 p.Leu558Ser ABCC7 p.Ile506Thr ABCC7 p.Gln1238* ABCC7 p.Ala559Thr ABCC7 p.Gly1061Arg ABCC7 p.Trp57* ABCC7 p.Ser589Ile Some have concentrated in the search of specific mutations that are Table 1 Mutations found in the Latin American CF patients Exon 1 p.L6VÌe; Exon 3 p.W57X, p.R75X, p.G85E Exon 4 p.R117H Exon 6a p.H199Y, p.V201M, p.L206W, p.Q220X, p.V232D, c.846delTÌe; Exon 6b p.Y275XÌe;, c.935delA Exon 7 p.R334W, p.R347P, p.Y362XÌe;, c.1078delT, c.1215delG Exon 8 c.1323_1324insAÌe; Exon 9 c.1460_1461delATÌe;, c.1353_1354insTÌe;,# Exon 10 p.I506T, p.I507del, p.F508del Exon 11 p.G542X, p.S549N, p.S549R, p.G551D, p.G551S, p.R553X, p.L558S, p.A559T, c.1782delA Exon 12 p.S589I Exon 13 p.H609RÌe;, p.P750L, p.V754M, c.1924_1930del, c.2055_2063del, c.2183AA NG;c.2184delA, c.2184delA, c.2185_2186insC, c.2347delG, c.2566_2567insTÌe;, c.2594_2595delGTÌe; Exon 14a p.R851L, c.2686_2687insTÌe; Exon 15 c.2869_2870insG Exon 16 c.3120+1GNA Exon 17a p.I1027T, c.3171delC, c.3199_3204del Exon 17b p.G1061R, p.R1066C, p.W1069X#, p.W1089X, p.Y1092X, p.W1098CÌe; Exon 19 p.R1162X, p.W1204X, p.Q1238X, c.3617_3618delGAÌe;#, c.3659delC Exon 20 p.W1282X, p.R1283M Exon 21 p.N1303K, c.4016_4017insT Exon 22 c.4160_4161insGGGGÌe; 5' flanking c.-834GNT Intron 2 c.297-1GNAÌe;, c.297-2ANG Intron 3 c.406-1GNA Intron 4 c.621+1GNT Intron 5 c.711+1GNT Intron 8 c.IVS8-5T Intron 10 c.1716GNA, c.1717-1GNA Intron 11 c.1811+1.6KbANG, c.1812-1GNA Intron 12 c.1898+1GNA, c.1898+3ANG Intron 14 c.2789+2_2789+3insA, c.2789+5GNA Intron 17a c.3272-26ANG Intron 17b c.3500-2ANGÌe; Intron 19 c.3849+1GNA, c.3849+10KbCNT Intron 20 c.4005+1GNA, c.4005-1GNA# Mutations are listed according to their position in the gene. Login to comment 46 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp ABCC7 p.Gly85Glu ABCC7 p.Gln220* ABCC7 p.His199Tyr ABCC7 p.Val232Asp ABCC7 p.Val201Met ABCC7 p.Arg75* ABCC7 p.Ile506Thr ABCC7 p.Trp57* of chromosomes analysed p.F508del p.G542X p.W1282X p.N1303K p.R1162X p.L6VÌe; p.W57X p.R75X p.G85E p.R117H p.H199Y p.V201M p.L206W p.Q220X p.V232D p.Y275XÌe; p.R334W p.R347P p.Y362XÌe; p.I506T Argentina 98 61 440 258 18 12 12 2 1 1 3 1 5 1 310 181 20 7 5 5 7 0 5 0 222 135 15 7 5 1 26 14 2 1 1 150 88 6 6 1 2 3 Subtotal and frequency (%) 1246 100 737 59.15 61 4.90 27 2.17 28 2.25 9 0.72 1 0.08 1 0.08 13 1.04 1 0.08 13 1.04 1 0.08 Brazil 468 221 26 11 74 38 2 1 320 155 28 3 8 8 4 1 2 1 1 8 122 62 120 38 10 3 148 38 4 0 0 48 15 154 75 5 1 0 2 0 386 154 24 6 10 17 9 0 10 1 18 4 0 0 2 0 0 0 0 Subtotal and frequency (%) 1858 100 800 43.06 99 5.33 11 0.59 34 1.83 25 1.35 13 0.70 1 0.05 2 0.11 1 0.05 1 0.05 20 1.07 1 0.05 Chile 72 21 36 11 3 0 44 22 4 3 1 1 100 45 7 5 0 2 0 2 0 Subtotal and frequency (%) 252 100 99 41.28 14 5.55 8 3.17 3 1.19 3 1.19 Colombia 184 77 7 2 1 2 1 34 13 2 1 1 Subtotal and frequency (%) 218 100 90 41.28 9 4.13 3 1.38 2 0.92 2 0.92 1 0.46 Costa Rica Frequency (%) 48 100 11 22.91 12 25.00 0 0 0 0 0 Cuba Frequency (%) 144 100 49 34.03 Ecuador 32 11 1 50 16 2 2 20 5 0 0 0 Subtotal and frequency (%) 102 100 32 31.37 2 1.96 1 0.98 2 1.96 Mexico 194 79 12 4 3 1 1 1 2 80 36 4 1 Subtotal and frequency (%) 274 100 115 41.97 16 5.84 5 1.82 3 1.09 1 0.36 1 0.36 1 0.36 2 0.73 Uruguay Frequency (%) 76 100 43 56.58 6 7.89 2 2.63 3 3.95 3 3.95 2 2.63 Venezuela 54 16 2 82 41 Subtotal and frequency (%) 136 100 57 41.91 2 1.47 Total 4354 2033 221 49 72 42 1 1 3 32 1 1 1 2 1 1 1 39 1 1 2 Frequency (%) 100 46.69 5.08 1.13 1.65 0.96 0.02 0.02 0.07 0.73 0.02 0.02 0.02 0.05 0.02 0.02 0.02 0.90 0.02 0.02 0.05 The five most frequent mutations are shown on the left-hand side, followed by the rest of the mutations in 5'-3' and exon-intron order. Login to comment 51 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Gly551Ser ABCC7 p.Val754Met ABCC7 p.Ser549Arg ABCC7 p.Ser549Asn ABCC7 p.Arg1066Cys ABCC7 p.Tyr1092* ABCC7 p.Arg1283Met ABCC7 p.Ile1027Thr ABCC7 p.Arg851Leu ABCC7 p.Trp1089* ABCC7 p.Pro750Leu ABCC7 p.Trp1204* ABCC7 p.Leu558Ser ABCC7 p.Gln1238* ABCC7 p.Ala559Thr ABCC7 p.Gly1061Arg ABCC7 p.Ser589Ile Table 2 p.I507del p.S549N p.S549R p.G551D p.G551S p.R553X p.L558S p.A559T p.S589I p.H609RÌe; p.P750L p.V754M p.R851L p.I1027T p.G1061R p.R1066C p.W1069X# p.W1089X p.Y1092X p.W1098CÌe; p.W1204X 3 0 1 0 1 1 1 1 1 0 4 1 2 3 1 3 0.24 1 0.08 1 0.08 6 0.48 2 0.16 1 0.08 1 0.08 4 0.32 1 0.08 1 4 1 2 1 1 0 0 0 1 0 0 0 1 1 0 1 0 2 0 1 3 0 0 0 0 0 0 1 0.05 1 0.05 1 0.05 10 0.54 1 0.05 2 0.11 3 0.16 3 0 0 0 1 0 1 1 2 0.79 4 1.58 4 1 1 1 1 4 1.83 1 0.46 1 0.46 1 0.46 1 0.46 0 0 0 0 0 0 0 5 5 1 1 1 1 1 1 1 1 1 1 1 5 1.82 6 2.19 1 0.36 1 0.36 1 0.36 1 0.36 1 0.36 1 0.36 1 0.36 1 0.36 1 0.36 1 0.36 1 1.31 1 1.31 1 1.31 10 6 6 6 1 22 1 1 2 1 1 1 1 1 1 6 1 3 5 1 1 0.23 0.14 0.14 0.14 0.02 0.51 0.02 0.02 0.05 0.02 0.02 0.02 0.02 0.02 0.02 0.14 0.02 0.07 0.11 0.02 0.02 (continued on next page) Table 2 Mutation frequencies in Latin American CF patients Country p.Q1238X p.R1283M c.-834GNT c.297-1GNA* c.297-2ANG c.406-1GNA c.621+1GNT c.711+1GNT c.846delT* c.935delA c.1078delT c.1215delG c.1323_1324insA* c.1353_1354insT*# c.1460_1461delAT* Argentina 1 3 1 1 1 1 1 Subtotal and frequency (%) 1 0.08 1 0.08 4 0.32 1 0.08 1 0.08 1 0.08 Brazil 1 1 1 1 0 0 Subtotal and frequency (%) 1 0.05 2 0.11 1 0.05 Chile 0 0 Subtotal and frequency (%) Colombia 1 1 Subtotal and frequency (%) 1 0.46 1 0.46 Costa Rica Frequency (%) 0 Cuba Frequency (%) Ecuador Subtotal and frequency (%) Mexico 1 3 1 2 1 1 Subtotal and frequency (%) 1 0.36 3 1.09 1 0.36 1 0.36 2 0.73 1 0.36 Uruguay Frequency (%) 1 1.31 Venezuela Subtotal and frequency (%) Total 1 1 1 1 1 3 7 2 1 2 1 1 1 1 1 Frequency (%) 0.02 0.02 0.02 0.02 0.02 0.07 0.16 0.05 0.02 0.05 0.02 0.02 0.02 0.02 0.02 (continued ) Table 2 c.1716GNA c.1717-1GNA c.1782delA c.1811+1,6KbANG c.1812-1GNA c.1898+1GNA c.1898+3ANG c.1924_1930del c.2055_2063del c.2183AANG;c.2184delA c.2184delA c.2185_2186insC 5 1 4 1 1 1 0 1 2 2 6 0.48 1 0.08 6 0.48 2 0.16 1 0.08 1 0.08 1 0.08 1 0 6 5 1 3 0 0 0 0 7 0.37 5 0.27 1 0.05 3 0.16 0 0 12 1 12 5.50 1 0.46 0 0 1 1 2 2 1 0.36 1 0.36 2 0.73 2 0.73 1 1.31 1 14 1 18 5 3 1 1 2 6 1 1 0.02 0.32 0.02 0.41 0.11 0.07 0.02 0.02 0.05 0.14 0.02 0.02 (continued on next page) Table 2 Mutation frequencies in Latin American CF patients Country c.2347delG c.2566_2567insT* c.2594_2595delGT* c.2686_2687insT* c.2789+2_2789+3insA c.2789+5GNA c.2869_2870insG c.3120+1GNA c.3171delC c.3199_3204del c.3272-26ANG c.3500-2ANG* Argentina 2 1 2 2 3 3 1 1 2 Subtotal and frequency (%) 2 0.16 1 0.08 2 0.16 2 0.16 6 0.48 1 0.08 1 0.08 2 0.16 Brazil 2 1 1 1 6 0 0 4 0 Subtotal and frequency (%) 2 0.11 1 0.05 1 0.05 10 0.54 1 0.05 Chile Subtotal and frequency (%) Colombia 1 1 1 Subtotal and frequency (%) 1 0.46 1 0.46 1 0.46 Costa Rica Frequency (%) Cuba Frequency (%) Ecuador Subtotal and frequency (%) Mexico 2 Subtotal and frequency (%) 2 0.73 Uruguay Frequency (%) 1 1.31 Venezuela Subtotal and frequency (%) Total 2 2 1 3 2 9 1 12 1 2 2 1 Frequency (%) 0.05 0.05 0.02 0.07 0.05 0.21 0.02 0.28 0.02 0.05 0.05 0.02 (continued ) Table 2 c.3617_3618delGA*,# c.3659delC c.3849+1GNA c.3849+10kbCNT c.4005+1GNA c.4005-1GNA# c.4016_4017insT c.4160_4161insGGGG* c.IVS8-5T Unknown Authors 37 Aulehla-Scholz [17] 2 4 1 2 4 76 Visich [12] 1 78 Iba&#f1;ez [18] 54 Varela 2004 8 Prieto [19] 2 1 1 1 18 Oller-Ramirez 2004 4 0.32 6 0.48 1 0.08 1 0.08 2 0.16 5 0.40 271 21.75 205 Raskin [20] 32 Chiba [21] 1 89 Bernardino [22] 60 Marostica [23] 69 Parizotto [24] 99 Cabello [25,26] 33 Martins [27] 70 Streit [28] 0 5 120 Raskin [15] 0 0 12 Goloni-Bertollo [29] 1 0.05 5 0.27 789 42.46 48 Rios [30] 22 Molina [31] 1 11 Navarro [32] 0 3 34 Repetto [33] 4 1.58 115 45.63 1 67 Keyeux [14] 17 Restrepo [34] 1 0.46 84 38.53 0 25 52.08 Venegas [35] 95 65.97 Collazo [36] 20 Merino [37] 30 Cassiman 2004 15 Paz-y-Mino [38] 65 63.72 1 1 53 Orozco [13] 2 35 Villalobos [39] 3 1.09 1 0.36 88 32.11 11 14.47 Luzardo [40,41] 36 Restrepo [34] 41 Alvarado [42] 77 56.62 1 4 1 18 1 1 2 1 5 1620 0.02 0.09 0.02 0.41 0.02 0.02 0.05 0.02 0.11 37.21 Mutation frequencies in Latin American CF patients most frequently found in Caucasians, by allele specific polymerase chain reaction (AS-PCR), enzymatic digestion, allele specific oligonucleotide hybridization (ASO), or using mainly commercial kits, whereas other studies used a systematic approach to analyse the promoter, coding and exon/ intron boundaries of the CFTR region in the search for any possible mutation. Login to comment 62 ABCC7 p.Gly542* The p.G542X mutation, with a total frequency of 5.07% (25% in Costa Rica to 1.47% in Venezuela), is the second most frequent mutation in Latin America, with the exception of Colombia and Costa Rica. Login to comment 63 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Arg1162* p.N1303K, p.W1282X and p.R1162X are the next most frequent mutations, with variations from 0.59% to 3.95% (Table 3). Login to comment 64 ABCC7 p.Gly542* Costa Rica is a unique case, where p.G542X (12/48 chromosomes) and p.F508del (11/48 chromosomes) have almost the same frequencies. Login to comment 66 ABCC7 p.Gly85Glu The p.G85E mutation was found in several countries such as Argentina [[12,18,19], Oller Ramirez, personal communication], Brazil [15,22], Ecuador (Cassiman, 2004, personal communication), Mexico [13] and Uruguay [41] with frequencies ranging from 0.36% in Mexico up to 3.95% in Uruguay. Login to comment 69 ABCC7 p.Arg334Trp ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn As shown in Table 4, 19 of them have overall frequencies of 0.1% to 1% in Latin America and could be considered as rare, but some of them have local elevated frequencies, like c.1811+1.6KbANG in Colombia (from 4.2% to 10.5% in the different geographical regions studied) [14, 46], p.G85E in Ecuador (8.9%) (Ruiz et al., personal communication), Uruguay (3.95%) [41], Brazil (2.33%) [15] and Argentina (2.26%) [18], p.R334W in Brazil (2.6%) [15, 22] and p.I507del (2.58%) and p.S549N (2.5%) in Mexico [13] (Table 2). Login to comment 70 ABCC7 p.Arg1162* p.R1162X showed an overall frequency of 0.96% (Table 3), but with some regional elevated frequencies, like in Santa Catarina, Brazil, with a presence of 10.4% in the sample studied [15]. Login to comment 73 ABCC7 p.Gly551Asp The p.G551D mutation, which shows an elevated frequency in the world, was found only in one Argentinean [18], two Brazilian [20,25], two Chilean [33, 32] and one Mexican [13] patient. Login to comment 74 ABCC7 p.Arg117His p.R117H, a frequent mutation in the British patients, was investigated in the patients from Argentina [[18], Varela and Targovnik, personal communication], Brazil [15,28,29], Colombia [14], Costa Rica [35] and Mexico [13], and was found only in one CF patient from Mexico. Login to comment 78 ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Trp1316* ABCC7 p.Arg347His ABCC7 p.Asp1270Asn ABCC7 p.Arg352Gln ABCC7 p.Gln493* ABCC7 p.Val520Phe ABCC7 p.Tyr122* ABCC7 p.Arg560Thr ABCC7 p.Arg1158* ABCC7 p.Ser1255* ABCC7 p.Lys710* ABCC7 p.Gln890* ABCC7 p.Ser1196* ABCC7 p.Glu60* ABCC7 p.Gly178Arg ABCC7 p.Trp1310* ABCC7 p.Tyr563Asp ABCC7 p.Cys524* ABCC7 p.Ser364Pro ABCC7 p.Gly330* At least another 38 mutations have been searched for, but none of them were found in the CF patients from Latin America: p.E60X, p.Y122X, p.G178R, p.G330X, p.R347H, p.R352Q, p.S364P, p.A455E, p.Q493X, p.V520F, p.C524X, p.R560T, p.Y563D, p.P574H, p.K710X, p.Q890X, p. R1158X, p.S1196X, p.S1255X, p.D1270N, p.W1310X, p. W1316X, c.405+1G-A, c.444delA, c.556delA, c.574delA, c.1677delTA, c.2043delG, c.2307insA, c.2909delT, c.3120G-A, c.3358delAC, c.3662delA, c.3750delAG, c.3791delC, c.3821delT, c.3849+4A-G, c.3905insT. Login to comment 85 ABCC7 p.Gly542* Costa Rica sits on an isolated branch, apparently due to the weight given by the exceptionally high frequency of the p.G542X mutation in these patients (25%). Login to comment 89 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* Table 3 Most frequent mutations (N1%) in Latin American patients Country Chromosomes analysed p.F508del p.G542X p.N1303K p.W1282X p.R1162X Unknown n % n % n % n % n % n % Argentina 1246 737 59.15 61 4.90 28 2.25 27 2.17 9 0.72 271 21.75 Brazil 1858 800 43.06 99 5.33 34 1.83 11 0.59 25 1.35 789 42.46 Chile 252 99 39.28 14 5.55 0 0.00 8 3.17 3 1.19 115 45.63 Colombia 218 90 41.28 9 4.13 2 0.92 3 1.38 2 0.92 84 38.53 Costa Rica 48 11 22.92 12 25.00 - - - - - - 25 52.08 Cuba 144 49 34.03 - - - - - - - - 95 65.97 Ecuador 102 32 31.37 2 1.96 1 0.98 - - - - 65 63.72 Mexico 274 115 41.97 16 5.84 5 1.82 - - - - 88 32.11 Uruguay 76 43 56.58 6 7.89 2 2.63 - - 3 3.95 11 14.47 Venezuela 136 57 41.91 2 1.47 - - - - - - 77 56.62 Total 4354 2033 46.69 221 5.08 72 1.65 49 1.13 42 0.96 1620 37.21 A - sign indicates that these mutations were not tested in the sample of patients, therefore their real frequency remains unknown. Login to comment 90 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Arg1066Cys ABCC7 p.Tyr1092* Table 4 Mutations with frequencies between 0.1% and 1% Mutation Frequency Country Number of chromosomes % p.R334W 39 0.90 Argentina, Brazil, Chile, Colombia, Uruguay p.G85E 32 0.73 Argentina, Brazil, Ecuador, Mexico, Uruguay p.R553X 22 0.51 Argentina, Brazil, Chile, Mexico, Uruguay c.1811+1.6KbANG 18 0.41 Argentina, Colombia c.3849+10KbCNT 18 0.41 Argentina, Mexico c.1717-1GNA 14 0.32 Argentina, Brazil, Uruguay c.3120+1GNA 12 0.28 Argentina, Brazil Colombia p.I507del 10 0.23 Brazil, Mexico, Uruguay c.2789+5GNA 9 0.21 Argentina, Brazil, Colombia, Uruguay c.621+1GNT 7 0.16 Argentina, Brazil, Mexico p.S549N 6 0.14 Mexico p.S549R 6 0.14 Argentina, Brazil, Colombia p.G551D 6 0.14 Argentina, Mexico p.R1066C 6 0.14 Argentina, Colombia, Mexico c.2183ANG;c.2184delA 6 0.14 Argentina, Mexico p.Y1092X 5 0.11 Colombia, Mexico c.1812-1GNA 5 0.11 Brazil c.IVS8-5T 5 0.11 Argentina c.3659delC 4 0.09 Argentina Unfortunately, at present not all Latin-American countries have started molecular studies in their patients with a probable Cystic Fibrosis diagnosis. Login to comment 98 ABCC7 p.Arg117His ABCC7 p.Gly551Ser ABCC7 p.Arg347Pro ABCC7 p.Val754Met ABCC7 p.Leu206Trp ABCC7 p.Gln220* ABCC7 p.His199Tyr ABCC7 p.Arg1283Met ABCC7 p.Ile1027Thr ABCC7 p.Val232Asp ABCC7 p.Arg851Leu ABCC7 p.Val201Met ABCC7 p.Pro750Leu ABCC7 p.Arg75* ABCC7 p.Trp1204* ABCC7 p.Leu558Ser ABCC7 p.Ile506Thr ABCC7 p.Gln1238* ABCC7 p.Ala559Thr ABCC7 p.Gly1061Arg ABCC7 p.Trp57* ABCC7 p.Ser589Ile As an example, in the case of Argentina and Uruguay, the p.F508del mutation shows the highest frequencies (59% and Table 5 Mutations with frequencies less than 0.1% Panel A Mutation Number of chromosomes % Country p.R75X 3 0.07 Mexico c.W1089X 3 0.07 Argentina, Brazil c.406-1GNA 3 0.07 Mexico c.1898+1GNA 3 0.07 Argentina, Brazil c.2686_2687insTÌe; 3 0.07 Argentina, Brazil p.L206W 2 0.05 Brazil p.I506T 2 0.05 Mexico p.S589I 2 0.05 Argentina c.711+1GNT 2 0.05 Argentina c.935delA 2 0.05 Mexico c.2055_2063del 2 0.05 Mexico c.2347delG 2 0.05 Brazil c.2566_2567insTÌe; 2 0.05 Argentina c.2789+2_2789+3insA 2 0.05 Argentina c.3199_3204del 2 0.05 Mexico c.3272-26ANG 2 0.05 Argentina c.4016_4017insT 2 0.05 Argentina Panel B Mutation N % each Country p.L6VÌe;, p.W57X, p.Q220X, p.Y362XÌe;, p.I1027T, p.G1061R, p.R1283M, c.297-2ANG, c.1353_1354insTÌe;, c.1460_1461delATÌe;, c.1782delA, c.1898+3ANG, c.2184delA, c.2594_2595delGTÌe;, c.2869_2870insG, c.4005Ìe;1GNA, c.4005-1GNA# 17 0.02 Argentina p.R117H, p.H199Y, p.G551S, p.L558S, p.P750L, p.V754M, p.W1069X#, p.W1098CÌe;, p.W1204X, c.297-1GNAÌe;, c.846delTÌe;, c.1078delT, c.1716GNA, c.1924_1930del, c.4160_4161insGGGGÌe; 15 0.02 Mexico p.V201M, p.V232D, p.Y275XÌe;, p.R347P, p.R851L, p.Q1238X, c.3171delC, c.3617_3618delGAÌe;# 8 0.02 Brazil p.A559T, p.H609RÌe;, c.1215delG, c.1323_1324insAÌe;, c.2185_2186insC, c.3500-2ANGÌe;, c.3849+1GNA, 7 0.02 Colombia c.-834GNT 1 0.02 Uruguay The upper part (Panel A) shows the mutations found in more than one patient, whereas the lower part (Panel B) of the table shows all the mutations that are present only once in each country. Login to comment 101 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* Furthermore, if we take three of the most frequent mutations in Europeans (p.F508del, p.G542X and p. N1303K), along with a very frequent mutation in Italians, p.R1162X [9], the percentage of these in Argentinean and Uruguayan CF patients adds up 67% and 71%, respectively, of the mutations (Table 3). Login to comment 110 ABCC7 p.Ala559Thr Actually, two African mutations (p.A559T and c.3120+1GNA) have been found in two regions with high African admixture in Colombia (Bolivar and Antioquia-Choc&#f3;) [14], and the c.3120+1G-NA mutation has also been found in Brazil [15, 26], with a frequency of 4% in Rio de Janeiro, and Argentina (Oller Ramirez, personal communication). Login to comment 111 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys 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.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Arg75* As discussed, another way to disclose similarities or differences in the distribution of mutations in the CF patients from Latin Table 6 Screening panel of CFTR mutations Country Total number of mutations Minimum panel Detection power Uruguay 12 6 mutations: p.F508del, p.G542X, p.R1162X, p.N1303K (p.R334W, p.G85E) 78% Argentina 52 7 mutations: p.F508del, p.G542X, p.R1162X, p.W1282X, p.N1303K (p.R334W, p.G85E) 71% M&#e9;xico 35 8 mutations: p.F508del, p.G542X, p.N1303K (p.R75X, p.I507del, p.S549N,c.406-1GNA, c.3849+10kbGNA) 58% Colombia 19 7 mutations: p.F508del, p.G542X, p.R1162X, p.W1282X, p.N1303K (p.S549R, c.1811+1.6kbANG) 56% Brazil 41 6 mutations: p.F508del, p.G542X, p.R1162X, p.W1282X, p.N1303K (p.R334W) 53% The total number of mutations found in each country is indicated in the second column from left. Login to comment 126 ABCC7 p.Gly542* In this country, p. G542X (25%) is the first mutation, followed by p.F508del (22.92%) (Table 3). Login to comment 127 ABCC7 p.Gly542* As argued by the authors, this unusual high frequency of p.G542X, which is almost four times that observed overall in Spain (7.66%) and Andalusia (8.6%) [9], could be a consequence of a strong founding effect due to the small number of settling families from this region established in Costa Rica in the XVIth-XVIIth century. Login to comment 134 ABCC7 p.Arg334Trp ABCC7 p.Gly85Glu This panel, besides the common mutations shown in Table 3, should include the p.R334W and p.G85E mutations. Login to comment 139 ABCC7 p.Arg553* From a clinical point of view, a first screen should include the main mutation panel described in Table 6, after which a locally (geographically) adapted choice of other relevant regions of the CFTR gene to be screened (particular mutations, or exons and exon/intron boundaries) seems advisable in those patients where the genotype remains unknown after the basic panel screening, like for instance the p.R553X mutation in Sao Paulo [20] and Formosa (Varela and Targovnik, personal communication), since otherwise an important proportion of mutations in these patients could be overlooked. Login to comment