ABCMdb

PMID: 1380689

Liechti-Gallati S, Bonsall I, Malik N, Schneider V, Kraemer LG, Ruedeberg A, Moser H, Kraemer R
Genotype/phenotype association in cystic fibrosis: analyses of the delta F508, R553X, and 3905insT mutations.
Pediatr Res. 1992 Aug;32(2):175-8., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553* The relation between the cystic fibrosis mutations .6.F508, R553X, and 3905insT and clinical parameters such as sweat test electrolytes, age at chronic Pseudomonas aeruginosa COlonization, Chrispin-Norman x-ray scores, and relative underweight have been investigated in 45 patients homozygous for .6.F508 (.6.F2), in 12 compound heterozygotes for .6.F508/R553X (.6.F1/ RX1), in three R553X homozygotes (RX2), and in 13 patients compound heterozygous for .6.F508/3905insT (.6.F16). Login to comment 6 ABCC7 p.Arg553* The significant results as wellas some trends regarding the relative underweight demonstrate a milder clinical course in R553X heterozygotes and more severe disease in the .6.F16 group compared to .6.F508 homozygotes. Login to comment 7 ABCC7 p.Arg553* The three patients homozygous for R553X presented with a two-stage course showing mild progression before P. aeruginosa infection and as severe a course as the .6.F16 patients after P. aeruginosa colonization at the age of 12 y. Login to comment 30 ABCC7 p.Arg553* We previously reported on DNA marker haplotypes of restriction fragment length polymorphisms flanking the CF gene as well as on l>F508 and R553X frequencies in CF families of Switzerland (20, 21). Login to comment 42 ABCC7 p.Arg553* The new detected 3905insT mutation of exon 20 (manuscript in preparation) and the R553X mutation have turned out to be the second and third most common mutations in Switzerland, showing strong linkage to haplotype 6 and 3, respectively. Login to comment 43 ABCC7 p.Arg553* ABCC7 p.Arg553* Three patients presenting with genotype 33 were homozygous for R553X (RX2), 12 demonstrated heterozygosity for DoF508 and R553X (DoFI /RX I), and 13 patients were compound heterozygous for DoF508 and 3905insT related to haplotype 6 (DoFI6). Login to comment 44 ABCC7 p.Arg553* The following data and figures present the relation between parameters of the clinical course and the specific CF mutations DoF508, R553X, and 3905insT. Login to comment 60 ABCC7 p.Arg553* The presence of R553X and 3905insT was tested by amplification of exons II and 20 followed either by digestion of the amplification product by the restriction enzyme HincH or by sequencing of the single-stranded polymerase chain reaction product. Login to comment 73 ABCC7 p.Arg553* However, the tendencies are the same as for x-ray scores: ~F 16 patients are the most underweight, and R553X patients develop mild underweight during the 1st decade, but thereafter dramatically increase the underweight up to 28.7% at the age of 20 y (Table 2). Login to comment 79 ABCC7 p.Arg553* ABCC7 p.Arg553* Our data demonstrate that patients carrying two R553X mutations present with the latest onset of P. aeruginosainfection of all genetic subgroups and that ~F508/R553X compound heterozygotes show significantly later onset than do t.F508 homozygotes (Fig. IA ). Login to comment 81 ABCC7 p.Arg553* Although the role of P. aeruginosa colonization in the pathogenesis of lung disease in CF is still not clear (26), we found some relationship between the age at P. aeruginosa onset and a significant increase of x-ray scores in t.F508 as well as R553X homozygous patients (Table I). Login to comment 88 ABCC7 p.Arg553* Homozygosity for R553X means later onset ofinfection (12.0 y; range 6.217.3 y; n = 3) than homozygosity for ~F508 (6.7 y; range 0.217.4 y; n = 35). Login to comment 93 ABCC7 p.Arg553* and compound heterozygotes for t.F508 and R553X (t.FI/RXI; e ); B, t. F508 homozygotes (t.F2; .) Login to comment 94 ABCC7 p.Arg553* and compound heterozygotes for t.F508 and 3905insT (t.FI6; A); and C, compo und heterozygotes for t.F508 and R553X (t.FI / RX I; e ) and compound heterozygotes for t.F508 and 3905insT (t.FI6; A). Login to comment 101 ABCC7 p.Arg553* ABCC7 p.Arg553* The nonsense mutation R553X seems to decrease the influence of the i1F508 deletion in i1F508/R553X heterozygotes, causing a milder course and slowed progression (Fig. lA, Tables 1 and 2). Login to comment 102 ABCC7 p.Arg553* The two compound heterozygous groups i1FI/RXI and i1FI6 indicate dominant effects of both the R553X (Fig. IB, Table 1) and 3905insT (Fig. Ie, Table 1) mutations compared with i1F508. Login to comment 104 ABCC7 p.Arg553* In their 1st decade, the three patients homozygous for R553X confirm this hypothesis. Login to comment