ABCMdb

PMID: 17331079

Alonso MJ, Heine-Suner D, Calvo M, Rosell J, Gimenez J, Ramos MD, Telleria JJ, Palacio A, Estivill X, Casals T
Spectrum of mutations in the CFTR gene in cystic fibrosis patients of Spanish ancestry.
Ann Hum Genet. 2007 Mar;71(Pt 2):194-201., [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC7 p.Gly542* Specific geographic distributions for the most common mutations, p.F508del, p.G542X, c.1811 + 1.6kbA > G and c.1609delCA, were confirmed. Login to comment 9 ABCC7 p.Val232Asp Furthermore, two other relatively common mutations (p.V232D and c.2789 + 5G > A) showed uneven geographic distributions. Login to comment 45 ABCC7 p.Trp1282* ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp ABCC7 p.Gly85Glu ABCC7 p.Arg1066Cys ABCC7 p.Lys710* ABCC7 p.Gln890* ABCC7 p.Val232Asp ABCC7 p.Ala1006Glu ABCC7 p.Ala1006Glu ABCC7 p.Val562Ile (%) p.F508del # E.10 1009 (51.74) p.G542X # E.11 150 (7.69) p.N1303K # E.21 57 (2.92) c.1811 + 1.6kbA > G I.11 36 (1.84) p.R334W # E.7 35 (1.79) p.L206W E.6a 32 (1.64) c.711 + 1G > T # I.5 31 (1.58) p.Q890X E.15 28 (1.43) p.R1162X # E.19 25 (1.28) c.2789 + 5G > A # I.14b 24 (1.23) p.R1066C E.17b 23 (1.18) p.I507del # E.10 21 (1.07) c.1609delCA E.10 18 (0.92) c.712-1G > T I.5 18 (0.92) c.3272-26A > G I.17a 18 (0.92) c.2183AA > G # E.13 16 (0.82) p.G85E # E.3 15 (0.77) c.2869insG E.15 15 (0.77) p.W1282X # E.20 15 (0.77) p.V232D E.6a 14 (0.71) p.A1006E * E.17a 12 (0.61) c.2184insA E.13 11 (0.56) p.K710X E.13 11 (0.56) TOTAL (n = 23) 1,634 (83.72) * , the complex allele [p.A1006E; p.V562I; IVS8-6(5T)] #, CF mutations identified with the Celera Diagnosis Cystic Fibrosis v2 genotyping assay and the Inno-Lipa CFTR12, CFTR17 + Tn Samples with microsatellite haplotypes 16/45-46-47 (IVS8CA/IVS17bTA) were submitted to direct analysis of the c.1811 + 1.6kbA > G mutation, which was found mainly associated with the 16-46 haplotype. Login to comment 52 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Gly1244Glu ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Pro205Ser ABCC7 p.Glu585* ABCC7 p.Glu1308* ABCC7 p.Ser549Arg ABCC7 p.Arg1158* ABCC7 p.Thr1299Ile ABCC7 p.Met1101Lys ABCC7 p.Tyr1092* ABCC7 p.His199Tyr ABCC7 p.Ser945Leu ABCC7 p.Asp1152His ABCC7 p.Gln30* ABCC7 p.His1085Arg ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg851Leu ABCC7 p.Trp1089* ABCC7 p.Leu558Ser ABCC7 p.Ser50Pro ABCC7 p.Phe1074Leu ABCC7 p.Arg1070Trp ABCC7 p.Glu92Lys ABCC7 p.Tyr1014Cys ABCC7 p.Arg851* ABCC7 p.Gly673* ABCC7 p.Gln98Arg ABCC7 p.Gln1281* ABCC7 p.Leu365Pro ABCC7 p.Arg709* ABCC7 p.Trp361Arg ABCC7 p.Trp57* ABCC7 p.Leu571Ser ABCC7 p.Ala561Glu ABCC7 p.Thr582Arg ABCC7 p.Trp202* ABCC7 p.Lys536* ABCC7 p.Gln1100Pro ABCC7 p.Arg560Gly ABCC7 p.Glu60Lys ABCC7 p.Gly85Val ABCC7 p.Gln1313* ABCC7 p.Leu159Ser ABCC7 p.Asp924Asn ABCC7 p.Gly1244Val ABCC7 p.Leu1254* ABCC7 p.Val1008Asp ABCC7 p.Ala399Asp ABCC7 p.Glu692* ABCC7 p.Leu1065Arg ABCC7 p.Tyr1381* Mutation 0.46-0.35 9 c.1078delT #, p.R347P # 8 p.G85V, c.621 + 1G > T #, p.S549R (T > G) #, p.R553X #, c.3849 + 10kbC > T # 7 p.R347H #, c.1812-1G > A, p.R709X 0.30-0.10 6 p.H199Y, p.P205S, 5 p.R117H #, p.G551D #, p.W1089X, p.Y1092X, CFTR50kbdel 4 c.296 + 3insT, c.1717-1G > A #, c.1949del84, c.3849 + 1G > A 3 p.E92K, c.936delTA, c.1717-8G > A, c.1341G > A, p.A561E, c.2603delT, p.G1244E, [p.D1270N; p.R74W] 2 p.Q2X, p.P5L, CFTRdele2,3, p.S50P, p.E60K, c.405 + 1G > A, c.1677delTA, p.L558S, p.G673X, p.R851X, p.Y1014C, p.Q1100P, p.M1101K, p.D1152H, CFTRdele19, p.G1244V, p.Q1281X, p.Y1381X <0,1 1 c.124del23bp, p.Q30X, p.W57X, c.406-1G > A, p.Q98R, p.E115del, c.519delT, p.L159S, c.711 + 3A > T, p.W202X, c.875 + 1G > A, p.E278del, p.W361R, c.1215delG, p.L365P, p.A399D, c.1548delG, p.K536X, p.R560G, c.1782delA, p.L571S, [p.G576A; p.R668C], p.T582R, p.E585X, c.1898 + 1G > A, c.1898 + 3A > G, c.2051delTT, p.E692X, p.R851L, c.2711delT, c.2751 + 3A > G, c.2752-26A > G, p.D924N, p.S945L, c.3121-1G > A, p.V1008D, p.L1065R, [p.R1070W; p.R668C], [p.F1074L; 5T], p.H1085R, p.R1158X, c.3659delC #, c.3667del4, c.3737delA, c.3860ins31, c.3905insT #, c.4005 + 1G > A, p.T1299I, p.E1308X, p.Q1313X, c.4095 + 2T > A, rearrangements study (n = 4) Mutations identified in CF families with mixed European origin: c.182delT, p.L1254X, c.4010del4. Login to comment 53 ABCC7 p.Leu206Trp ABCC7 p.Arg1066Cys ABCC7 p.Gln890* #, CF mutations identified with the Celera Diagnosis Cystic Fibrosis v2 genotyping assay and the Inno-Lipa CFTR12, CFTR17 + Tn p.L206W, p.Q890X and p.R1066C, presented with frequencies above 1%, while 51 mutations (42%) were found only once (Table 2). Login to comment 60 ABCC7 p.Leu1254* Furthermore, three different CF mutations, c.182delT, p.L1254X and c.4010del4, were identified in affected offspring among couples with mixed European origin. Login to comment 61 ABCC7 p.Gly542* The evaluation data from the specific regions contributing to this study showed that the c.2789 + 5G > A mutation was, along with p.G542X, the second most common mutation (9/86, 10.5%) among the Balearic Islands` alleles, whereas mutation c.1609delCA had its highest prevalence in Aragon (10/109, 9%). Login to comment 62 ABCC7 p.Val232Asp Two mutations, p.V232D and c.1341G > A, showed the same high frequency (3/122, 2.5%) in the Castilla-Leon region. Login to comment 66 ABCC7 p.Ala1006Glu ABCC7 p.Ser50Pro ABCC7 p.Phe1074Leu For example the IVS8-6(5T) allele was detected in cis with four different mutations (p.S50P, c.2751 + 3A > G, p.A1006E and p.F1074L). Login to comment 67 ABCC7 p.Val754Met ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Ile148Thr ABCC7 p.Ser549Arg ABCC7 p.Thr1299Ile ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Ile1027Thr ABCC7 p.Arg1070Trp Seven other complex alleles were observed: [c.296 + 3insT; p.V754M], [p.F508del; p.I1027T], [p.S549R; -102T > A], [p.G576A; p.R668C], [p.R1070W; p.R668C], [p.D1270N; p.R74W] and [p.T1299I; p.I148T]. Login to comment 68 ABCC7 p.Leu206Trp In addition, the p.L206W mutation was always found to be associated with the rare haplotype 9T-9TG, and the c.1811 + 1.6kbA > G mutation with the c.3601-111G > C polymorphism. Login to comment 70 ABCC7 p.Ala1006Glu ABCC7 p.Ala1006Glu ABCC7 p.Ala1006Glu ABCC7 p.Ala1006Glu ABCC7 p.Val562Ile ABCC7 p.Val562Ile The major complexity detected is attributable to the polyvariant [p.A1006E; p.V562I; IVS8-6(5T)], which was observed in all patients with the p.A1006E mutation (Table 1). Login to comment 76 ABCC7 p.Leu206Trp ABCC7 p.Arg1066Cys ABCC7 p.Gln890* It is not surprising that four of the common mutations, presenting with frequencies above 1% (c.1811 + 1.6kbA > G, p.L206W, p.Q890X and p.R1066C), were undetected by these panels (Table 1). Login to comment 84 ABCC7 p.Leu206Trp Comparing this mutation update with our previous report (Casals et al. 1997), we observed that some mild mutations, c.2789 + 5G > A and p.L206W, should now be considered as common mutations (relative frequency >1%). Login to comment 85 ABCC7 p.Val232Asp ABCC7 p.Ala1006Glu In addition, three other mild mutations, c.3272-26A > G, p.V232D and p.A1006E, showed frequencies ranging from 0.9% to 0.6% (Table 1). Login to comment 90 ABCC7 p.Gly542* The p.F508del mutation showed frequencies ranging from 86% (North) to 46% (South) in the Iberian Peninsula (Casals et al. 1992; Coto et al. 1994; Borrego et al. 1994; Telleria et al. 1999) as well as a 14% prevalence of the p.G542X mutation in the Mediterranean Coastal area (Casals et al. 1993). Login to comment 93 ABCC7 p.Val232Asp In addition, two other relatively frequent mutations showed unequal geographic distributions, p.V232D in the Castilla-Leon region (2.5%) and c.2789 + 5G > A in the Balearic Islands (10.5%). Login to comment 94 ABCC7 p.Gly542* In fact, this splicing mutation has also been reported with frequencies ≥ 1% in France (Claustres et al. 2000), Italy (Bonizzato et al. 1995), Greece (Kanavakis et al. 2003) and Turkey (Kilinc et al. 2002), suggesting that, like p.G542X, c.2789 + 5G > A was spread across the Mediterranean Sea. Login to comment 99 ABCC7 p.Gly542* Some high frequencies such as those found for the p.G542X mutation have been attributed to the Spanish ancestry of the Mexican (Orozco et al. 2000) and Brazilian (Bernardino et al. 2000) populations. Login to comment 105 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Arg1066Cys ABCC7 p.Gln890* ABCC7 p.Arg75* ABCC7 p.Ile506Thr Our impression is that Table 3 Common CF mutations identified in this study and in several Latin American populations Mutation This study Hispanic1 Mexico2 Colombia3 Brazil4 Argentina5 Chile6 p.F508del 51.7 51.6 40.7 41.8 48.4 58.6 45.0 p.G542X 7.7 4.0 6.2 3.8 8.8 4.1 7.0 p.N1303K 2.9 0.8 2.0 0.5 2.5 2.7 - c.1811 + 1,6kbA > G 1.8 - - 6.5 - 0.9 - p.R334W 1.8 1.6 - 0.5 2.5 1.1 2.0 p.L206W 1.6 - - - 0.6 - - c.711 + 1G > T 1.6 - - - - - - p.Q890X 1.4 - - - - - - p.R1162X 1.3 0.8 - 1.1 2.5 0.4 2.0 c.2789 + 5G > A 1.2 - - 0.5 0.3 0.7 - p.R1066C 1.2 1.6 - 0.5 - 0.2 - p.I507del 1.0 - 2.6 - - 0.7 - c.2183AA > G 0.8 - 1.0 - 0.2 - p.G85E 0.7 0.8 0.5 - 1.3 0.7 - p.W1282X 0.7 0.8 - 1.1 1.3 2.7 5.0 c.3849 + 10kbC > T 0.4 4.0 0.5 - - 0.9 3.0 p.S549N - 2.4 2.6 - - - - c.3120 + 1G > A - 1.6 - 0.5 - - - c.3876delA - 5.6 - - - - - c.406-1G > A - 1.6 1.5 - - - - c.935delA - 1.6 1.0 - - - - p.R75X - 0.8 1.5 - - - - c.2055del9 - - 1.0 - - - - p.I506T - - 1.0 - - - - c.3199del6 - - 1.0 - - - - p.S549R 0.4 - - 2.2 - 0.2 - c.1717-1G > A 0.2 - - - 0.3 1.1 - p.G551D 0.2 0.8 0.5 - - - 1.0 p.R553X 0.4 - 0.5 - 0.6 0.2 1.0 No. Login to comment