ABCMdb

PMID: 17137500

Kraemer R, Baldwin DN, Ammann RA, Frey U, Gallati S
Progression of pulmonary hyperinflation and trapped gas associated with genetic and environmental factors in children with cystic fibrosis.
Respir Res. 2006 Nov 30;7:138., [PubMed]

Sentences

No. Mutations Sentence Comment

87 ABCC7 p.Arg553* ABCC7 p.Arg553* Compound heterozygotes for the nonsense mutation R553X and ∆F508 constituted group 3 with the third most common genotype (R553X/∆F: n = 10 6.6%), whereas the fourth group comprised 43 miscellaneous genotypes (28.3%). Login to comment 98 ABCC7 p.Arg553* RespiratoryResearch2006,7:138http://respiratory-research.com/content/7/1/138 Page5of15 (pagenumbernotforcitationpurposes) Table 1: Patient cohort, data base characteristics, distribution of CFTR mutations, and stratification into different types of bronchial infection in study patients with cystic fibrosis Patient (from database*) Follow-up statistic (from database*) n % number of tests age ranges covered all 152 total 1460 6 to 10 y 80% - males 77 50.7 per child 10 (4-15) 11 to 15 y 71% - females 75 49.3 per year 83(29-116) 16 to 20 y 39% CFTR mutation stratification n % ∆F508(2) 86 56.6 Miscellaneous: numbers in brackets 3905insT/∆F 13 8.6 ∆F508 and1717-1G>A(4), W1282X(4), 2347delG(3), G524X(2), Q525X(2), N1303K(2), 621+1G>T(1), R553X/∆F 10 6.6 2176insC(1), 394delTT(1), 4005+1G-A(1). Login to comment 99 ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* 420del9(1), E585X(1), G126D(1), G85E(1), R347P(1), 1078delT(1); Miscellaneous 43 28.3 3905insT and1717-1G>A(1),K710X(1), M1101K(1), Q39X(1), P5L(1), R553X(1); R553X andR553X(1); G542X and T5(3), G542X(1); Q542X and3732delA(2); N1303K and2347delG(1), 2789+5G>A(1); 1199delG andR560S(1). Login to comment 125 ABCC7 p.Arg553* Children in whom the R553X/∆F mutation was present demonstrated the lowest values for all lung function parameters at time of initial measurement (age 6 to 8 yrs). Login to comment 161 ABCC7 p.Arg553* sign. FRCpleth ∆F508(2) 0.151 1.117 n.s. 3.979 0.008 3905insT/∆F 0.215 1.057 0.048 0.09154 R553X/∆F 0.165 0.120 n.s. 0.09969 LCI ∆F508(2) 0.247 5.077 0.002 0.491 n.s. 3905insT/∆F 0.291 1.865 0.006 0.200854 R553X/∆F 0.278 0.307 n.s. 0.236018 VTG ∆F508(2) 0.198 3.372 0.019 6.499 0.0001 3905insT/∆F 0.233 1.036 0.011 0.113801 R553X/∆F 0.256 0.065 n.s. 0.128347 sReff ∆F508(2) 0.405 0.849 n.s. 10.043 0.0001 3905insT/∆F 0.549 1.297 n.s. 0.305402 R553X/∆F 0.741 3.298 0.039 0.328812 FEV1 ∆F508(2) -0.185 4.542 0.004 13.066 0.0001 3905insT/∆F -0.216 2.502 0.009 0.16809 R553X/∆F -0.466 0.431 n.s. 0.18238 FEF50 ∆F508(2) -0.439 1.774 n.s. 14.255 0.0001 3905insT/∆F -0.738 1.011 n.s. 0.30235 R553X/∆F -1.029 2.952 0.002 0.32759 Misc -0.354 * adjusted for multiple comisons according Bonferroni their ventilatory requirements at rest by increasing breathing frequency rather than tidal volume in order to minimize the increase of resistive work associated with thoracic wall excursion. Login to comment 198 ABCC7 p.Arg553* In comparison to the inframe homozygotes ∆F508(2) and nonsense R553X/∆F compound heterozygotes, patients carrying one frameshift mutation 3905insT have a poorer prognosis with respect to the onset of pulmonary disease, progression of lung function, and mortality [87]. Login to comment 200 ABCC7 p.Arg553* We undertook a similar statistical approach to evaluate potential associations between repeated lung function measurements and the most frequent CFTR genotypes in Switzerland, ∆F508(2), 3905insT/∆F and R553X/∆F. Login to comment 201 ABCC7 p.Arg553* Significant differences in lung function indices were identified between the 3905insT/∆F compound heterozygote and ∆F508(2) homozygote mutation groups for FRCpleth, LCI and VTG, as well as between R553X/∆F compound heterozygotes and ∆F508(2) homozygotes for sReff, and FEF50 (Table 3). Login to comment 202 ABCC7 p.Arg553* Confirming previous findings [15,21,51,88,89], our data demonstrate that the 3905insT mutation is associated with severe lung disease, manifesting early in life [21], whereas the R553X/∆F mutation seems to provide milder pulmonary involvement during the first 5 to 6 yrs of life, thereafter however, to be exposed to a much more pronounced progression compared with both the ∆F508 and the 3905insT/∆F. Login to comment 204 ABCC7 p.Arg553* The effect is even more pronounced for the R553X/∆F group. Login to comment