PMID: 15994263

de Gracia J, Mata F, Alvarez A, Casals T, Gatner S, Vendrell M, de la Rosa D, Guarner L, Hermosilla E
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.
Thorax. 2005 Jul;60(7):558-63., [PubMed]
Sentences
No. Mutations Sentence Comment
185 ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 15994263:185:58
status: NEW
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ABCC7 p.Ala455Glu
X
ABCC7 p.Ala455Glu 15994263:185:48
status: NEW
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Although there are a few rare mutations such as A455E and R117H which are clearly linked to a better pulmonary outcome,12 13 the effect on the lungs of F508del and most other mutations cannot be separated and attempts to link mutations in CFTR to severity of lung disease have been unsuccessful.14 Furthermore, genes other than CFTR and environmental factors such as access to specialised centres and treatment strategies may be more important factors in modifying the development, progression, and severity of pulmonary disease. Login to comment
209 ABCC7 p.Gly551Asp
X
ABCC7 p.Gly551Asp 15994263:209:587
status: NEW
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ABCC7 p.Gly551Asp
X
ABCC7 p.Gly551Asp 15994263:209:1070
status: NEW
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ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 15994263:209:640
status: NEW
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ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 15994263:209:1376
status: NEW
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ABCC7 p.Trp1282*
X
ABCC7 p.Trp1282* 15994263:209:424
status: NEW
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ABCC7 p.Trp1282*
X
ABCC7 p.Trp1282* 15994263:209:872
status: NEW
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ABCC7 p.Arg334Trp
X
ABCC7 p.Arg334Trp 15994263:209:633
status: NEW
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ABCC7 p.Arg334Trp
X
ABCC7 p.Arg334Trp 15994263:209:1103
status: NEW
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ABCC7 p.Arg334Trp
X
ABCC7 p.Arg334Trp 15994263:209:1360
status: NEW
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ABCC7 p.Arg347His
X
ABCC7 p.Arg347His 15994263:209:647
status: NEW
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ABCC7 p.Arg347His
X
ABCC7 p.Arg347His 15994263:209:1121
status: NEW
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ABCC7 p.Arg347His
X
ABCC7 p.Arg347His 15994263:209:1391
status: NEW
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ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 15994263:209:522
status: NEW
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ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 15994263:209:1016
status: NEW
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ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 15994263:209:1253
status: NEW
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ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 15994263:209:1508
status: NEW
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ABCC7 p.Asn1303Lys
X
ABCC7 p.Asn1303Lys 15994263:209:1531
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15994263:209:377
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15994263:209:866
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15994263:209:933
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15994263:209:1041
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15994263:209:1083
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15994263:209:1133
status: NEW
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ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 15994263:209:1151
status: NEW
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ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 15994263:209:405
status: NEW
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ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 15994263:209:881
status: NEW
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ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 15994263:209:900
status: NEW
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ABCC7 p.Arg1162*
X
ABCC7 p.Arg1162* 15994263:209:1007
status: NEW
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ABCC7 p.Asp1270Asn
X
ABCC7 p.Asp1270Asn 15994263:209:579
status: NEW
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ABCC7 p.Pro205Ser
X
ABCC7 p.Pro205Ser 15994263:209:661
status: NEW
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ABCC7 p.Pro205Ser
X
ABCC7 p.Pro205Ser 15994263:209:1089
status: NEW
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ABCC7 p.Leu206Trp
X
ABCC7 p.Leu206Trp 15994263:209:626
status: NEW
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ABCC7 p.Leu206Trp
X
ABCC7 p.Leu206Trp 15994263:209:1344
status: NEW
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ABCC7 p.Arg1066Cys
X
ABCC7 p.Arg1066Cys 15994263:209:539
status: NEW
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ABCC7 p.Arg1066Cys
X
ABCC7 p.Arg1066Cys 15994263:209:1270
status: NEW
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ABCC7 p.Gln890*
X
ABCC7 p.Gln890* 15994263:209:442
status: NEW
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ABCC7 p.Gln890*
X
ABCC7 p.Gln890* 15994263:209:1097
status: NEW
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ABCC7 p.Asp836Tyr
X
ABCC7 p.Asp836Tyr 15994263:209:654
status: NEW
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ABCC7 p.Asp836Tyr
X
ABCC7 p.Asp836Tyr 15994263:209:1407
status: NEW
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To study the decline in pulmonary function between groups the ANOVA method (repeated measures) was used with baseline and current spirometric values as dependent variables, genotype groups as the independent variable, and age and evolution time as Table 1 CFTR mutation according to functional classification Class Molecular dysfunction Mutation I Defective protein production G542X, 711+1GRT, 1609delCA, R1162X, 1717-8GRA, W1282X, 1782delA, Q890X, 1898+3ARG, CFTRdele19, 936delTA II Defective protein processing F508del, N1303K, I507del, R1066C III Defective protein regulation D1270N, G551D IV Defective protein conductance L206W, R334W, R117H, R347H, D836Y, P205S V Partially defective production or processing 2789+5GRA, 1811+1.6kbARG, 3849+10kbCRT, 3272+26GRA Table 2 Groups based on genotype in CF adult patients Functional classes Genotype No of subjects I-I G542X/W1282X 1 R1162X/1898+3ARG 1 R1162X/CFTRdele19 1 I-II F508del/G542X 5 F508del/711+1GRT 2 F508del/1717-8GRA 1 F508del/936delTA 1 F508del/R1162X 1 N1303K/1609delCA 1 I-III G542X/D1270N+R74W 1 711+1G-T/G551D 1 I-IV G542X/P205S 1 Q890X/R334W 1 1609delCA/R347H 1 I-V G542X/2789+5GRT 2 G542X/1811+1.6kbARG 1 1782delA/2789+5GRA 1 1609delCA/1811+1.6kbARG 1 II-II F508del/F508del 21 F508del/N1303K 1 F508del/R1066C 1 II-III F508del/D1270N+R74W 1 I507del/D1270N+R74W 1 II-IV F508del/L206W 4 F508del/R334W 3 F508del/R117H 3 F08del/R347H 2 F508del/D836Y 1 II-V F508del/2789+5GRA 5 F508del/3849+10kbCRT 2 F508del/1811+1.6kbARG 2 F508del/3272+26GRA 1 N1303K/1811+1.6kbARG 1 N1303K/2789+5GRA 1 adjusted variables. Login to comment
220 ABCC7 p.Arg347His
X
ABCC7 p.Arg347His 15994263:220:168
status: NEW
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ABCC7 p.Asp836Tyr
X
ABCC7 p.Asp836Tyr 15994263:220:149
status: NEW
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Sweat tests were positive (sweat chloride concentration >60 mEq/l) in all but three patients (pair of CFTR mutations: I507del/ D1270N+1274W, F508del/D836Y, and F508del/R347H, respectively). Login to comment
251 ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 15994263:251:149
status: NEW
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ABCC7 p.Ala455Glu
X
ABCC7 p.Ala455Glu 15994263:251:142
status: NEW
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ABCC7 p.Pro67Leu
X
ABCC7 p.Pro67Leu 15994263:251:185
status: NEW
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The mild pulmonary phenotype seen in patients with genotype I-II/III-V is consistent with previous reports where a few rare mutations such as A455E, R117H, 3849+10kbCRT, 2789+5GRT, and P67L (all class IV or V mutations) are clearly linked to a better pulmonary outcome.13 14 26-28 The findings observed in this study support the hypothesis that differences in CF pulmonary phenotype could be related to the effect of the genotype on CFTR protein production and function. Nevertheless, it is important to recognise that specific mutations may have characteristics of more than one 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 20 30 40 50 60 Follow up (years) Events Lung transplant Dead I-II/I-II 9 6 I-II/III-V 1 0 Genotype I-II/III, IV or V I-II/I-II p<0.001 (Log-rank test for trend) Figure 3 Kaplan-Meier survival curves by genotype. Login to comment
264 ABCC7 p.Arg117His
X
ABCC7 p.Arg117His 15994263:264:245
status: NEW
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They found that patients who were homozygous for F508del have significantly higher overall mortality and higher crude mortality adjusted for sex and age than those who were homozygous for mutation class IV and V or heterozygous for F508del with R117H, 3849+10kbCRT and 2789+5GRT. Login to comment
272 ABCC7 p.Gly551Asp
X
ABCC7 p.Gly551Asp 15994263:272:30
status: NEW
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ABCC7 p.Asp1270Asn
X
ABCC7 p.Asp1270Asn 15994263:272:19
status: NEW
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Only the mutations D1270N and G551D were analysed and they were associated with a more favourable outcome of pulmonary function. Nevertheless, previous studies have pointed out that, among functional class III mutations, there may exist a wide variability in their phenotypes that depends principally on the CFTR protein site for which they code.33 34 In summary, the results of this study suggest that the genotype, based on functional class mutation on the two chromosomes, seems to be one of the most decisive factors for pulmonary phenotype and for survival in relation to pulmonary damage. Login to comment