ABCMdb

PMID: 16275171

Braun AT, Farrell PM, Ferec C, Audrezet MP, Laxova A, Li Z, Kosorok MR, Rosenberg MA, Gershan WM
Cystic fibrosis mutations and genotype-pulmonary phenotype analysis.
J Cyst Fibros. 2006 Jan;5(1):33-41. Epub 2005 Nov 4., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Gly551Asp ABCC7 p.Gly1047Arg Results: Two novel alleles were discovered, namely G1047R and 1525-2AYG, which were accompanied by F508del and G551D mutations, respectively. Login to comment 6 ABCC7 p.Arg347Pro However, patients with class IV mutations (e.g., R347P) or with pancreatic sufficiency showed serial chest radiographs that were atypically mild. Login to comment 79 ABCC7 p.Gly1047Arg Thereafter, the longitudinal patterns of WCXR and BCXR for the two patients with novel mutations (i.e., G1047R and 1525-2AYG) were superimposed on the Table 1 Summary of patient characteristics Characteristics F508del homozygote group (n =38) Pancreatic sufficiency groupa (n =19) Sex Male 25 8 Female 13 11 Center Madison 21 12 Milwaukee 17 7 Group Screened 38 3 Control 0 14 Other 0 2 Meconium ileus Yes 6 0 No 32 19 Mean age at diagnosis (weeks)TS.D. 7.15T2.4 193.1T192 Mean sweat Cl mEq/lTS.D. Login to comment 80 ABCC7 p.Arg117His ABCC7 p.Arg347Pro ABCC7 p.Gly542* ABCC7 p.Arg352Gln ABCC7 p.Arg117Cys ABCC7 p.Arg1066His ABCC7 p.Gly1047Arg Thereafter, the longitudinal patterns of WCXR and BCXR for the two patients with novel mutations (i.e., G1047R and 1525-2AYG) were superimposed on the Table 1 Summary of patient characteristics Characteristics F508del homozygote group (n =38) Pancreatic sufficiency groupa (n =19) Sex Male 25 8 Female 13 11 Center Madison 21 12 Milwaukee 17 7 Group Screened 38 3 Control 0 14 Other 0 2 Meconium ileus Yes 6 0 No 32 19 Mean age at diagnosis (weeks)TS.D. 7.15T2.4 193.1T192 Mean sweat Cl mEq/lTS.D. Login to comment 81 ABCC7 p.Arg117His ABCC7 p.Arg347Pro ABCC7 p.Gly542* ABCC7 p.Arg352Gln ABCC7 p.Arg117Cys ABCC7 p.Arg1066His 101.0T9.5 83.5T21.2 CXR scores at diagnosis WCXR 2.48T32b 4.68T71 BCXR 21.9T0.3 21.1T.48 Pulmonary function at 8 years FEV1 (%)c 97T4 104T2 FVC (%)c 103T3 103T2 FEV1/FVC% 0.92T0.03 0.98T.01 FEF25 - 75% 99T11 104T5 a Mild pancreatic phenotype mutations include: R117H occurring with F508del (n =5) and G542X (n =1); R117C with F508del (n =2); R347P with F508del (n =1), R1066H (n =1) and 2184insA (n À1), 2789+5G>A with F508del (n =3); 3272À26A>G with F508del (n =1); 3849+10kbC>T with F508del (n =1); L138ins with 3272À26A>G (n =1); R352Q with F508del (n =1); and 1336K with F508del (n =1). Login to comment 100 ABCC7 p.Gly1047Arg Two novel mutations for North American CF patients were discovered during our investigation process, namely G1047R (patient #1) and 1525-2AYG (patient #2). Login to comment 101 ABCC7 p.Gly1047Arg Two novel mutations for North American CF patients were discovered during our investigation process, namely G1047R (patient #1) and 1525-2AYG (patient #2). Login to comment 118 ABCC7 p.Gly1047Arg G1047R describes a guanine to cytosine base-pair substitution in the 1047th codon which would lead to a missense mutation, changing glycine to arginine. Login to comment 119 ABCC7 p.Gly1047Arg G1047R describes a guanine to cytosine base-pair substitution in the 1047th codon which would lead to a missense mutation, changing glycine to arginine. Login to comment 121 ABCC7 p.Gly1047Arg The patient`s genotype of F508del/G1047R or class II/I would suggest a ''severe`` phenotype as both mutations lead to a loss of functional CFTR protein at the apical cell membrane. Login to comment 122 ABCC7 p.Gly1047Arg The patient`s genotype of F508del/G1047R or class II/I would suggest a ''severe`` phenotype as both mutations lead to a loss of functional CFTR protein at the apical cell membrane. Login to comment 125 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp Taking in to account the patient`s other mutation, G551D, the genotype of G551D/1525-2AYG would translate to a class III/I genotype and a prediction of ''severe`` disease manifestations, which is consistent with the MI presentation and early development of PI. Login to comment 126 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp Taking in to account the patient`s other mutation, G551D, the genotype of G551D/1525-2AYG would translate to a class III/I genotype and a prediction of ''severe`` disease manifestations, which is consistent with the MI presentation and early development of PI. Login to comment 129 ABCC7 p.Gly551Asp ABCC7 p.Gly1047Arg In addition, their spirometry results are also similar to the WCXR score 0 5 10 15 20 25 30 F508del/F508del Pancreatic sufficiency Patient 1 (F508del/G1047R) WCXR score 0 5 10 15 20 25 30 F508del/F508del Pancreatic sufficiency Patient 2 (G551D/1525-2A->G) 0 1 2 3 4 5 6 7 8 9 10 11 12 Age in years Fig. 3. Login to comment 130 ABCC7 p.Gly551Asp ABCC7 p.Gly1047Arg In addition, their spirometry results are also similar to the WCXRscore 0 5 10 15 20 25 30 F508del/F508del Pancreatic sufficiency Patient 1 (F508del/G1047R) WCXRscore 0 5 10 15 20 25 30 F508del/F508del Pancreatic sufficiency Patient 2 (G551D/1525-2A->G) 0 1 2 3 4 5 6 7 8 9 10 11 12 Age in years Fig. 3. Login to comment 149 ABCC7 p.Arg347Pro In contrast to patients #1 and #2, the longitudinal chest radiography data on patients with PS are different from the F508del homozygotes (e.g., R347P or 2789+5GYA as shown in Fig. 4). Login to comment 150 ABCC7 p.Arg347Pro ABCC7 p.Arg347Pro In contrast to patients #1 and #2, the longitudinal chest radiography data on patients with PS are different from the F508del homozygotes (e.g., R347P or 2789+5GYA as shown in Fig. 4). Login to comment 151 ABCC7 p.Arg347Pro In comparison with the longitudinal progression of the F508del homozygote group, the F508del/ R347P child obviously shows an atypical pattern of progression although she had slightly abnormal WCXR and BCXR scores when diagnosed at 6 weeks with sweat chloride values of 100 and 102 mEq/L. Login to comment 166 ABCC7 p.Arg347Pro A variety WCXR score 0 5 10 15 20 25 30 F508del/F508del Pancreatic sufficiency F508del/R347P Patient WCXR score 0 5 10 15 20 25 30 F508del/F508del Pancreatic sufficiency F508del/2789+5G->A Patient 0 1 2 3 4 5 6 7 8 9 10 11 12 Age in years Fig. 4. Login to comment 167 ABCC7 p.Arg347Pro A variety WCXRscore 0 5 10 15 20 25 30 F508del/F508del Pancreatic sufficiency F508del/R347P Patient WCXRscore 0 5 10 15 20 25 30 F508del/F508del Pancreatic sufficiency F508del/2789+5G->A Patient 0 1 2 3 4 5 6 7 8 9 10 11 12 Age in years Fig. 4. Login to comment 175 ABCC7 p.Gly1047Arg The two novel mutations (G1047R and 1525-2AYG) are named following accepted recommendations [34]. Login to comment 176 ABCC7 p.Gly1047Arg The two novel mutations (G1047R and 1525-2AYG) are named following accepted recommendations [34]. Login to comment