ABCMdb

PMID: 11484207

Orozco L, Gonzalez L, Chavez M, Velazquez R, Lezana JL, Saldana Y, Villarreal T, Carnevale A
XV-2c/KM-19 haplotype analysis of cystic fibrosis mutations in Mexican patients.
Am J Med Genet. 2001 Aug 15;102(3):277-81., 2001-08-15 [PubMed]

Sentences

No. Mutations Sentence Comment

43 ABCC7 p.Gly542* DF508 and G542X chromosomes (56% of all CF chromosomes) were highly associated with haplotype B (97.2% and 72.7%, respectively). Login to comment 46 ABCC7 p.Asn1303Lys ABCC7 p.Ser549Asn Among those found in more than one chromosome, S549N was associated only with haplotype A, N1303K only with haplotype B, DI507 only with D, and 2055del9!A only with A. Login to comment 47 ABCC7 p.Gly542* Carrier Detection XK haplotype analysis of families with at least one unknown CF allele or with uncommon mutations was TABLE I. Distribution of XK Haplotype on Cystic Fibrosis (CF) and Normal Chromosomes A B C D DF508 N 72 70 (97.2%) 2 (2.8%) G542X N 11 1 (9.09%) 8 (72.72%) 2 (18.18%) Others N 32 13 (40.6%) 5 (15.6%) 9 (28.1%) 5 (15.6%) Unknown N 33 18 (54.5%) 1 (3.0%) 13 (39.4%) 1 (3%) CF chromosomes N 148 32 (21.6%) 84 (56.7%) 22 (14.9%) 10 (6.8%) Normal N 110 54 (49.1%) 8 (7.3%) 35 (31.8%) 13 (11.8%) useful to determine the carrier status of siblings in 18 families (24.3%), as illustrated in Figure 1. Login to comment 51 ABCC7 p.Gly542* This difference is mainly due to the high frequency of mutations DF508 and G542X, associated with haplotype B in 97.2% and 72.7% of chromosomes, respectively. Login to comment 54 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys This ®gure is much lower than in European populations (48.8%) where several mutations such as G551D, N1303K, and W1282X are relatively frequent and associated with haplotype B (EWGCFG, 1990; Castaldo et al., 1996]. Login to comment 65 ABCC7 p.Arg117His ABCC7 p.Gly551Ser ABCC7 p.Asn1303Lys ABCC7 p.Ile148Thr ABCC7 p.Ser549Asn ABCC7 p.Arg75Gln ABCC7 p.Trp1098Cys ABCC7 p.Arg75* ABCC7 p.Trp1204* ABCC7 p.Leu558Ser ABCC7 p.Ile506Thr Distribution of XK Haplotype on Chromosomes Bearing Uncommon Cystic Fibrosis (CF) Mutations A B C D S549N 4/4 DI507 3/3 N1303K 3/3 2055 del9!A 2/2 I148T 1/1 406-1G!A 1/1 R75X 1/1 I506T 1/1 935delA 1/1 2183AA!G 1/1 1924del7 1/1 G551S 1/1 1078delT 1/1 R117H 1/1 384910KbC!T 1/1 1716G!A 1/1 W1204X 1/1 W1098C 1/1 846delT 1/1 R75Q 1/1 W1069X 1/1 L558S 1/1 4160insGGGG 1/1 297-1G!A 1/1 Fig. Login to comment 72 ABCC7 p.Gly542* G542X is the second most common CF mutation worldwide. Login to comment 74 ABCC7 p.Gly542* It has been suggested that G542X was introduced into Europe by the occidental Phoenicians 2,000 or 3,000 years ago [Loirat et al., 1997]. Login to comment 75 ABCC7 p.Gly542* In the Mexican population, G542X is also the second most common mutation (6.1%), and was found to be most frequently associated with haplotype B (72.2%), but also with haplotypes A (9.09%) and D (18.18%). Login to comment 77 ABCC7 p.Gly542* Recombination on the original G542X chromosome. Login to comment 82 ABCC7 p.Gly542* The fact that G542X was found in Native American populations of the U.S. Southwest such as the Pueblo [Grebe et al., 1992] supports the latter hypothesis. Login to comment 83 ABCC7 p.Arg1162* However, haplotype analysis of R1162X chromosomes suggested that racial admixture and genetic drift may have occurred in this isolated community [Mercier et al., 1994]. Login to comment 84 ABCC7 p.Ile148Thr As regards other mutations (Table II), DI507 was associated with haplotype D as previously described in southern France [Claustres et al., 1996]; I148T with haplotype B as described in Italy and southern France [Castaldo et al., 1996; Claustres et al., 1996]; and 1078delT with haplotype C as found in France [Claustres et al., 1996]. Login to comment 86 ABCC7 p.Ser549Asn Mutation S549N is relatively frequent in Mexico (2.5%) and was associated with haplotype A in all informative chromosomes. Login to comment 87 ABCC7 p.Ser549Asn As far as we know, there are no previous reports of XK haplotypes associated with S549N, which is very uncommon in other populations [CFGAC, 1994]. Login to comment 88 ABCC7 p.Asn1303Lys In contrast, we identi®ed one 384910kbC!T chromosome associated with haplotype C, as previously reported in Israel [Sereth et al., 1993], but differing from the Pueblo Amerindians, where this mutation was associated with haplotype A; the 2183AA!G chromosome was associated with haplotype D, but had been previously found on a B haplotype in Italy; N1303K was found on three haplotype B chromosomes, whereas in southern Europe this mutation has been associated mainly with haplotype B, but also with haplotypes A, C, and D [Petreska et al., 1998; Castaldo et al., 1996; Borrego et al., 1994; Claustres et al., 1996]. Login to comment