ABCMdb

PMID: 14641997

Raskin S, Pereira L, Reis F, Rosario NA, Ludwig N, Valentim L, Phillips JA 3rd, Allito B, Heim RA, Sugarman EA, Probst CM, Faucz F, Culpi L
High allelic heterogeneity between Afro-Brazilians and Euro-Brazilians impacts cystic fibrosis genetic testing.
Genet Test. 2003 Fall;7(3):213-8., [PubMed]

Sentences

No. Mutations Sentence Comment

11 ABCC7 p.Gly551Asp ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Although the major mutation causing CF accounts for 66% of mutant chromosomes screened worldwide, at least 1,000 sequence alterations associated with the disease have been identified in the CFTR gene during the past years, and their frequencies vary between populations (Tsui, 1990, 1992; Cystic Fibrosis Genetic AnalysisConsortium,1994, 1999).Previously, we have shown allelic heterogeneity in Brazilian CF patients of European origin by screening for DF508 and another four common worldwide mutations (G542X, N1303K, G551D, and R553X). Login to comment 54 ABCC7 p.Gly542* ABCC7 p.Arg1162* Only three mutations have an overall frequency higher than 4%-DF508, G542X, and R1162X-and a fourth, 312011G R A, has a frequency of 2.6% in the Afro-Brazilian group. Login to comment 61 ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gly85Glu In this study, we also found that only four among 70 CFTR mutations included in the screening panel were present in CF patients born in the three different states of Brazil and in the two population subgroups (Euro- and Afro-Brazilians) studied; that is, DF508, G542X, R1162X, and G85E. Login to comment 63 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Pro574His ABCC7 p.Pro574His ABCC7 p.Ala455Glu 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.Arg347Pro ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro ABCC7 p.Trp1316* ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Asp1270Asn ABCC7 p.Arg352Gln ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr ABCC7 p.Gln493* ABCC7 p.Gln493* ABCC7 p.Gln493* ABCC7 p.Val520Phe ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Tyr122* ABCC7 p.Arg560Thr ABCC7 p.Arg1158* ABCC7 p.Arg1158* ABCC7 p.Arg1158* ABCC7 p.Tyr1092* ABCC7 p.Tyr1092* ABCC7 p.Ser1255* ABCC7 p.Lys710* ABCC7 p.Lys710* ABCC7 p.Lys710* ABCC7 p.Gln890* ABCC7 p.Gln890* ABCC7 p.Gln890* ABCC7 p.Trp1089* ABCC7 p.Trp1089* ABCC7 p.Ser1196* ABCC7 p.Glu60* ABCC7 p.Gly178Arg ABCC7 p.Trp1310* ABCC7 p.Tyr563Asp ABCC7 p.Gln1238* ABCC7 p.Gln1238* ABCC7 p.Gln1238* ABCC7 p.Gln1238* ABCC7 p.Cys524* ABCC7 p.Ser364Pro ABCC7 p.Gly330* ABCC7 p.Ala559Thr FREQUENCIES OF 70 CFTR MUTATIONS IN DIFFERENT STATES OF BRAZIL, BY CONTINENTA L GROUP CFTR mutations SC PR MG detected n n n n % n % N % DF508 53 39 54 146 47.1 8 10.5 154 39.9 G542X 6 9 8 23 7.4 1 1.3 24 6.2 R1162X 9 2 4 15 4.8 2 2.6 17 4.4 N1303K 5 5 0 10 3.2 0 0 10 2.6 R334W 5 1 4 10 3.2 0 0 10 2.6 G85E 2 2 4 8 2.6 1 1.3 9 2.3 1717-1G®A 1 3 2 6 1.9 0 0 6 1.6 W1282X 4 1 1 6 1.9 0 0 6 1.6 3849110kbC®T 1 3 1 5 1.6 0 0 5 1.3 R553X 0 2 0 2 0.7 0 0 2 0.5 1812-1G®A 0 1 3 4 1.3 1 1.3 5 1.3 2183AA®G 2 1 0 3 1.0 0 0 3 0.8 312011G®A 0 0 2 2 0.7 2 2.6 4 1.0 Y1092X 0 1 1 2 0.7 1 1.3 3 0.8 G551D 0 0 0 0 0 0 0 0 0 W1089X 0 0 1 1 0.3 0 0 1 0.3 6211G®T 0 1 0 1 0.3 0 0 1 0.3 Q1238X 0 1 0 1 0.3 0 0 1 0.3 711-1G®T 0 1 0 1 0.3 0 0 1 0.3 R347P 1 0 0 1 0.3 0 0 1 0.3 189811G®A 1 0 0 1 0.3 0 0 1 0.3 I507 0 0 1 1 0.3 0 0 1 0.3 Subtotal 91 73 86 250 80.7 16 21.1 266 68.9 Alleles with CFTR 5 27 28 60 19.4 60 79.0 120 31.1 mutations not detected Total 96 100 114 310 100.0 76 100.0 386 100.0 Detection rate (%) 94.8 73.0 75.4 250 80.7 16 21.1 266 68.9 The following 70 CFTR mutations were selected and tested on the basis of frequency in various populations, known association with CF, or predicted deleterious effect on the CFTR protein product; DF508, G542X, N1303K, G551D, R553X, DI507, A455E, A559T, C524X, D1270N, E60X, G178R, G330X, G85E, 2307insA, I148T, K710X, P574H, Q1238X, Q493X, Q890X, R1158X, R1162X, R117H, R334W, R347H, R347P 2307insA, I148T, K710X, P574H, Q1238X, Q493X, Q890X, R1158X, R1162X, R117H, R334W, R347H, R347P 2307insA, 1148T, K710X, P574H, Q1238X, Q493X, Q890X, R1158X, R1162X, R117H, R334W, R347H, R347P, R352Q, R560T, S1196X, S1255X, S364P, S549N, S549R, V520F, W1089X, W1282X, W1310X, W1316X, Y1092X, Y122X, Y563D, 1078delT,1677delTA,1717-1G-A,1812-1G-A,1898 1 1G-A, 2043delG,2183delAA-G, 2184delA, 2789 1 5G-A, 2869insG, 2909delT, 3120 1 1G-A, 3120G-A, 3358delAC, 3659delC, 3662delA, 3750delAG, 3791delC, 3821delT, 3849 1 10KbC-T, 3849 1 4A-G, 3905insT, 405 1 1G-A, 444delA, 556delA, 574delA, 621 1 1G-T, and 711 1 1G-T. aSC, Santa Catarina State; PR, Parana State; MG, Minas Gerais State; n, number of chromosomes. Login to comment 69 ABCC7 p.Gly542* ABCC7 p.Gly542* G542X Our data show that G542X is the second most common CF mutation in two of the three Euro-Brazilian CF states studied (PR and MG), with an overall frequencyof 6.2% (Table 1). Login to comment 70 ABCC7 p.Gly542* The presence of G542X in the Afro-Brazilian group was, as for DF508, likely the result of Caucasian admixture, in agreement with North American data (Macek et al., 1997). Login to comment 71 ABCC7 p.Arg1162* R1162X This is the third most common mutation identified to date in the Euro-BrazilianCF patients overall, and the second most frequent in SC. Login to comment 73 ABCC7 p.Arg1162* Mutation R1162X is more common in southern than in northern Europe (Osborne et al., 1992; Cystic Fibrosis Genetic Analysis Consortium, 1994), and it has a very high frequency in those from specific regions of Italy, such as the region of Veneto (9%) and Trentino Alto Adige (14%) (Gasparini et al., 1992; Rendine et al., 1997). Login to comment 74 ABCC7 p.Arg1162* Interestingly, the parents of the CF patients born in SC carrying R1162X were all of Italian descent. Login to comment 77 ABCC7 p.Arg1162* The R1162X mutation is the second most common mutation identified to date in Afro-Brazilian CF patients (see Table 1). Login to comment 78 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu G85E With an overall frequency of 2.3%, G85E is the sixth most common mutation identified to date in the Euro-Brazilian and Afro-Brazilian CF patients, (2.6% and 1.3%, respectively). Login to comment 79 ABCC7 p.Gly85Glu Although G85E is not included in the 10 most frequent CF mutations worldwide (CFGAC, 1994) and neither is it among the five most frequent mutations in our sample, it is interesting to note that this mutation was found in all states and both population subgroups analyzed in this study, probably as the result of admixture with Euro-Brazilians. Login to comment 80 ABCC7 p.Gly551Asp ABCC7 p.Arg553* Two other mutations, R553X and G551D, are common worldwide, but are rare in Brazil. Login to comment 101 ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gly85Glu The presence in Afro-Brazilians of at least four CF alleles that are common in Caucasians (i.e., DF508, G542X, G85E, R1162X) indicates that the incidence of CF in Afro-Brazilians is due, at least in part, to genetic admixture. Login to comment