ABCMdb

PMID: 12357328

McCormick J, Green MW, Mehta G, Culross F, Mehta A
Demographics of the UK cystic fibrosis population: implications for neonatal screening.
Eur J Hum Genet. 2002 Oct;10(10):583-90., [PubMed]

Sentences

No. Mutations Sentence Comment

79 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gln493* ABCC7 p.Arg560Thr ABCC7 p.Tyr569Asp ABCC7 p.Tyr569Asp ABCC7 p.Arg709* ABCC7 p.Val456Ala ABCC7 p.Leu218* ABCC7 p.Leu218* It is envisaged that the proposed screening programme will be based on a three-stage protocol.6 In Table 3 Genotypes of the UK CF Caucasian and ISC populations Percentage of Percentage of genotyped UK CF genotyped UK CF Caucasian population ISC population Genotype n=4753 (%) n=78 (%) DF508/DF508 57.5 24.7 DF508/Unknown 11.5 3.5 DF508/G551D 5.1 0.0 DF508/G542X 2.8 0.0 Unknown/Unknown 2.7 27.1 DF508/621+1G?T 2.0 1.2 DF508/R117H 2.0 0.0 DF508/1898+1G?A 1.0 0.0 DF508/1717-G?A 0.9 0.0 DF508/N1303K 0.8 0.0 DF508 DI507 0.8 0.0 DF508/R553X 0.6 0.0 DF508/R560T 0.6 0.0 DF508/Q493X 0.5 0.0 G551D/Unknown 0.4 0.0 Other/Other 2.8 15.3* DF508/Other 6.7 0.0 Y569D/Y569D 0.0 8.2 L218X/L218X 0.0 3.5 1161delC/1161delC 0.0 3.5 R709X/V456A 0.0 2.4 G542X/G542X 0.4 2.4 Other/Unknown 1.0 3.5 The shaded areas represent the commonest genotypes in the ISC population. Login to comment 80 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Tyr569Asp ABCC7 p.Gln98* ABCC7 p.Gln98* ABCC7 p.Tyr569Cys *Includes 1525-1G?T/1525-1G?T, Y569C/Y569D, G551D/G551D, 1525-1G?A/1525-1G?A, R1162X/R1162X, R01/ 07/R01/07, 2184insA/2184insA, Y568D/Y568D, 1VSB1-1/1VSB1-1, 1506M/1506M, 3849+10kbC?T/3849+10kbC?T and Q98X/ Q98X. Login to comment 83 ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Ser549Asn ABCC7 p.Tyr122* The additional eleven are S549N, 3849+4A?G, 3905insT, 2789+5G?A, Y122X, 711+1G?T, R347P, R347H, R334W, A455E and 3281AA?G. Login to comment 84 ABCC7 p.Pro67Leu ABCC7 p.Tyr569Asp ABCC7 p.Glu60* ABCC7 p.Arg709* ABCC7 p.Leu218* The following seven mutations appear in Table 4 but not in the 31 mutation panel; 1154insTC, E60X, P67L, Y569D, L218X, 1161delC and R709X. Login to comment 85 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Gln493* ABCC7 p.Val520Phe ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Pro67Leu ABCC7 p.Tyr569Asp ABCC7 p.Glu60* ABCC7 p.Arg709* ABCC7 p.Leu218* Table 4 The commonest CFTR mutations in the UK Genotypes UK CF population Genotyped UK Caucasian CF Genotyped UK CF ISC (n=9866 chromosomes) population (n=9506 chromosomes) population (n=156 chromosomes) CFTR mutation gene frequency per 1000 genes gene frequency per 1000 genes gene frequency per 1000 genes DF508 741.0 752.0 294.9 G551D 33.7 34.3 12.8 G542X 18.5 18.4 25.6 R117H 12.5 12.7 0.0 621+1G?T 12.7 12.7 6.4 1717-1G?A 5.8 5.8 0.0 1898+1G?A 5.7 5.9 0.0 N1303K 5.6 5.4 0.0 DI507 4.8 5.0 0.0 R560T 4.2 4.3 0.0 R553X 3.3 3.4 0.0 1154insTC 3.2 3.3 0.0 Q493X 2.8 2.9 0.0 3659delC 2.8 2.9 0.0 E60X 2.4 2.4 0.0 W1282X 2.7 2.7 0.0 P67L 2.1 2.1 0.0 G85E 2.1 2.0 0.0 V520F 1.6 1.7 0.0 1078delT 1.3 1.4 0.0 Y569D 1.5 0.0 96.2 L218X 0.6 0.0 38.5 1161delC 0.7 0.1 38.5 R1162X 0.9 0.6 19.2 R709X 0.4 0.2 12.8 3849+10kbC?T 1.2 0.8 19.2 S549R* 0.6 0.0 0.0 *S549R mutations appear in the non-Caucasian but not the ISC subgroup. Login to comment 96 ABCC7 p.Gly551Asp ABCC7 p.Gly542* There are similar frequencies for the more common mutations between our UK Caucasian CF data (Table 4) and the Schwarz data (respectively, G551D 3.43% and 3.08%; G542X 1.84% and 1.68%; 621+1G?A 1.27% and 0.93%; 1717-1G?A 0.58% and 0.57%). Login to comment 97 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* In North America, DF508 accounts for 71.2%, with G542X (2.4%), G551D (2.4%), W1282X (1.4%), N1303K (1.3%) and R553X (0.9%).8 Genotype frequencies in CF have previously been shown to fit a Hardy - Weinberg model in a smaller regional UK study.9 In the current study, we find that the genotype frequencies only satisfy the Hardy-Weinberg equilibrium provided we exclude those without an identified CFTR mutation in the Other/Other category. Login to comment 101 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* When compared with a European CFTR geographic distribution,10 the UK CF patients possess a greater proportion of DF508, G551D and 621+1G?T mutations, and a smaller proportion of G542X, N1303K, W1282X and R1162X mutations. Login to comment 102 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* In France, the five most common genotypes were DF508/DF508 (47.8%), DF508 /G542X (3.4%), DF508/N1303K (2.7%), DF508 /1717-1G?A (2.1%) and DF508/2789+5G?A (1.5%) (Desgeorges M, personal communication) which is different to the commonest genotypes found in the UK population (Table 3). Login to comment 103 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg553* ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* N1303K and G542X occur at a frequency of around 5% in Italy.11 In Germany, a study of 658 CF families revealed mutation frequencies of R553X (1.8%), N1303K (1.3%), G542X (1.1%), G551D (0.8%) and R347P (0.8%).12 The frequency of CFTR mutations recorded for just over 1000 patients for the Irish CF Database include G551D in 7%, R117H in 2% and DF508 in 72% of patients.13 In the white South African population, a paper based on 192 patients found that DF508 accounts for 76% of the mutations with 3272-26A?G (4%), 394delTT (3.6%) and G542X (1.3%) the other most common mutations.14 It is suggested that the 3272-26A?G and 394delTT mutations are more common due to a founder effect in white South Africans of European descent. Login to comment