ABCMdb

ABCC7 p.Gly149Arg

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Publications

PMID: 16442101 [PubMed] Frelet A et al: "Insight in eukaryotic ABC transporter function by mutation analysis."

No. Sentence Comment

369 H139R, G149R, D192G and R258G in the two first CLs inhibited maturation and transport of CFTR to the cell surface. Login to comment

PMID: 10229049 [PubMed] Lecoq I et al: "Blood immunoreactive trypsinogen concentrations are genetically determined in healthy and cystic fibrosis newborns."

No. Sentence Comment

61 Twins or unrelated patients with identical genotype had very similar neonatal IRT concentrations: DF508/I148T (twins), 1040 and 1055 mg LÀ1 ; N1303K/G149R (twins), 1600 and 1725 mg LÀ1 ; DF508/E585X, 900 and 945 mg LÀ1 ; DF508/ G542X, 1535 and 1660 mg LÀ1 ; DF508/L206W, 980, 1090 and 1100 mg LÀ1 . Login to comment
72 In this study, CF newborns with one mutation in an exon encoding for either NBD1 or NBD2 (DF508, G542X, G551D, E585X, N1303K, etc.) and the other affecting one of the MSD (R117H, 574delA, I148T, G149R, L206W, etc.) had significantly lower IRT concentrations than CF neonates with both mutations located in NBD. Login to comment
76 I Lecoq et al. ACTA PÆDIATR 88 (1999) MSDs were associated with IRT concentrations lower than 1300 mg LÀ1 , with the exception of 574delA, 1078delT and G149R. Login to comment

PMID: 10736180 [PubMed] Chen EY et al: "Cystic fibrosis transmembrane conductance regulator has an altered structure when its maturation is inhibited."

No. Sentence Comment

202 G149R, like ∆F508, is a processing mutant with no detectable mature CFTR protein. Login to comment
224 Membranes were prepared from HEK cells transiently transfected with various CFTR cDNAs: WT, ∆F508, R297Q, H949Y, and G149R. Login to comment

PMID: 12794695 [PubMed] Timmreck LS et al: "Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina."

No. Sentence Comment

69 Mutations continue to be identified in association with CBAVD: A800G, G149R, R258G, E193K [Mercier et al., 1995], D1270N, and G576A [Ravnik-Glavac et al., 2000], to name a few. Login to comment

PMID: 12815607 [PubMed] Scotet V et al: "Comparison of the CFTR mutation spectrum in three cohorts of patients of Celtic origin from Brittany (France) and Ireland."

No. Sentence Comment

64 Spectrum of the CFTR Mutations Identified in the Cohorts from Brittany, Dublin Centre, and Cork Area Nucleotide Amino acid change * change Exon Number Frequency Number Frequency Number Frequency 211delG 2 1 0.1% 310G>T E60X 3 5 0.6% 4 0.3% 347C>A A72D 3 1 0.1% 368G>A W79X 3 1 0.1% 386G>A G85E 3 2 0.3% 3 0.2% 403G>A G91R 3 2 0.3% 482G>A R117H 4 4 0.5% 38 3.0% 4 1.4% 498T>A Y122X 4 1 0.1% 574delA 4 1 0.1% 577G>A G149R 4 1 0.1% 621+1G>T int 4 5 0.6% 21 1.7% 790C>T Q220X 6a 1 0.1% 875+1G>C int 6a 1 0.4% 905delG 6b 1 0.1% 1065C>G F311L 7 2 0.3% 1078delT 7 28 3.6% 1132C>T R334W 7 1 0.1% 1172G>A R347H 7 5 0.6% 1172G>T R347L 7 1 0.1% 1172G>C R347P 7 1 0.1% 1187G>A R352Q 7 3 0.2% 2 0.7% 1208A>G Q359R 7 1 0.1% 1154insTC 7 2 0.2% 1221delCT 7 2 0.3% 1248+1G>A int 7 1 0.1% 1249-27delTA int 7 1 0.4% 1334G>A W401X 8 1 0.1% 1461ins4 9 5 0.4% 1471delA 9 2 0.2% 1607C>T S492F 10 2 0.3% 1609C>T Q493X 10 1 0.1% 1648_1653delATC I507del 10 3 0.4% 10 0.8% 1 0.4% 1652_1655del 3 bp F508del 10 582 74.8% 966 76.5% 226 81.3% 1690G>T V520F 10 4 0.3% 1717-1G>A int 10 8 1.0% 9 0.7% 1756G>T G542X 11 5 0.6% 8 0.6% 1779T>G S549R 11 1 0.1% 1784G>A G551D 11 29 3.7% 82 6.5% 27 9.7% 1789C>G R553G 11 1 0.1% 1789C>T R553X 11 3 0.4% 1 0.1% 1806delA 11 1 0.1% 1811G>A R560K 11 2 0.3% 1811G>C R560T 11 30 2.4% 2 0.7% 1819T>A Y563N 12 1 0.1% 1853C>A P574H 12 1 0.1% 1898+1G>A int 12 1 0.1% 2184delA 13 1 0.1% 1 0.1% 2184insA 13 1 0.1% 2622+1G>A int 13 1 0.1% 2 0.2% 2622+1G>T int 13 1 0.1% 2623-2A>G ** int 13 1 0.1% 2670G>A W846X2 14a 8 1.0% 2752-1G>T int 14a 1 0.1% 2752-26A>G int 14a 2 0.2% 2789+5G>A int 14b 6 0.8% 2966C>T S945L 15 2 0.3% 3007delG 15 4 0.3% 3040G>C G970R 15 1 0.1% 3062C>T S977F 16 1 0.1% 3120+1G>A int 16 1 0.1% 3272-26A>G int 17a 4 0.5% 2 0.2% 2 0.7% 3320dupli(CTATG) 17b 1 0.1% 3329G>A R1066H 17b 1 0.1% 3340C>T R1070W 17b 1 0.1% 3408C>A Y1092X 17b 7 0.9% 3442G>T E1104X 17b 1 0.1% 3446T>G ** M1105R 17b 1 0.1% 3586G>C D1152H 18 1 0.1% 3601-17T>C + 1367delC int 18 + 9 1 0.1% 3616C>T R1162X 19 1 0.1% 2 0.2% 3659delC 19 2 0.2% 3832A>G I1234V 19 2 0.3% 3849+4A>G int 19 1 0.1% 3849+10kbC>T int 19 3 0.2% 3877G>A G1249R 20 1 0.1% 3884G>A S1251N 20 1 0.1% 3898insC 20 1 0.1% 3905insT 20 2 0.3% 3978G>A W1282X 20 3 0.4% 4005+1G>A int 20 6 0.8% 4016insT 21 1 0.1% 4041C>G N1303K 21 11 1.4% 5 0.4% 4136T>C L1335P 22 1 0.1% 1 0.4% 4279insA 23 1 0.1% Unidentified Unidentified - 3 0.4% 41 3.2% 11 4.0% Total 778 100.0% 1262 100.0% 278 100.0% * All nucleotide changes correspond to cDNA numbering. Login to comment

PMID: 12955726 [PubMed] Feldmann D et al: "CFTR genotypes in patients with normal or borderline sweat chloride levels."

No. Sentence Comment

8 R117H, D1152H, L206W, 3272-26A>G, S1235R, G149R, R1070W, S945L, and the poly-T tract variation commonly called IVS8-5T were also observed. Login to comment
44 Table 1 : Genotypes and Phenotypes of Patients with Normal or BordIerline Sweat Tests Patient Age at diagnosis (years) CFTR GENOTYPE* Allele 1 Allele 2 SWEAT CL- MEAN (MMOL/L) PHENOTYPE 1 0.2 F508del G149R 38 P+PI, neonatal hypertrypsinemia, 2 0.3 G551D R117H-7T 31 neonatal hypertrypsinemia 3 0.4 F508del R1070W 30.5 neonatal hypertrypsinemia 4 0.4 F508del R117H-7T 52 P 5 0.6 F508del 3849+10kbC>T 48 P 6 0.11 F508del S945L 58 P+PI 7 1 F508del 5T 40 P+CBAVD 8 2 F508del L206W 53 P 9 2 W1282X 5T 42.5 P 10 5 F508del 3849+10kbC>T 55.5 P 11 5 F508del L206W 55 P 12 5 G91R 5T 47.5 P 13 6 G551D S1235R+5T 49.5 P, neonatal hypertrypsinemia 14 7 F508del 3849+10kb 50 P, nasal popyposis 15 13 F508del R117H-7T 58 P, nasal polyposis 16 18 F508del 5T 60.5 P 17 20 G542X 3849+10kbC>T 52 P+PI 18 21 I507del 3849+10kbC>T 54 P, bronchiectasis 19 30 R347P 3849+10kbC>T 43 P, Pseudomonas colonisation 20 30 I507del L206W 57.5 CBAVD, chronic cough 21 31 F508del R117H-7T 60 CBAVD 22 32 G542X 3849+10kbC>T 30 P, Pseudomonas colonisation 23 34 F508del 3272-26A>G 64 P, CBAVD 24 37 R1070Q D1152H 56 CBAVD, bronchectasis 25 46 F508del D1152H 43 P 26 55 F508del D1152H 48 P, Pseudomonas colonisation 27 56 I507del S1235R 53 P 28 >18 F508del D1152H 60 P+PI 29 >20 F508del 3849+10kbC>T 18 P, bronchiectasis 30 >20 F508del 3272-26A>G 61 P *All mutations are named in accordance with the numbering used in the CFTR Mutation Database: http://www.genet.sickkids.on.ca/cftr/. Login to comment
101 The other mutations observed in trans of severe mutations were G149R, R1070W, S945L and S1235R. Login to comment
102 G149R and R1070W mutations have been previously described in CBAVD patients [Mercier et al., 1995; Jezequel et al., 2000] and S1235R have been described associated with variable pulmonary symptoms and occasionally borderline sweat tests [Monagham et al., 2000]. Login to comment

PMID: 16182665 [PubMed] Sarles J et al: "Combining immunoreactive trypsinogen and pancreatitis-associated protein assays, a method of newborn screening for cystic fibrosis that avoids DNA analysis."

No. Sentence Comment

44 A closer look at the results revealed that among the newborns with CF with moderately elevated IRT (50 to <100 ng/mL), 10 had genuine forms of the disease, their genotypes being DF508/DF508 (n = 6), DF508/P574H (n = 1), DF508/G542X (n = 1), DF508/G149R (n = 1), or DF508/? Login to comment

PMID: 16196493 [PubMed] Loo TW et al: "Rescue of DeltaF508 and other misprocessed CFTR mutants by a novel quinazoline compound."

No. Sentence Comment

26 Wild-type, ∆F508, H139R, G149R, R258G, S945L, and H949Y CFTR cDNAs were inserted into the pcDNA3 (Invitrogen, Oakville, ON) vector as described previously.13,14 Wild-type and mutant G268V P-gp cDNAs were inserted into the pMT21 vector (Genetics Institute) as described previously.15 Baby hamster kidney (BHK) cells stably expressing CFTR or P-gp were generated by cotransfection with cDNA and pWL-neo (Stratagene, Cedar Creek, TX). Login to comment
132 (C) BHK cells expressing misprocessed CFTR mutants H139R, G149R, R258G, S945L, H949Y, or wild-type CFTR were incubated for 48 h with (+) or without (-) 3 µM CFcor-325. Whole cell extracts were subjected to immunoblot analysis with a rabbit polyclonal antibody against CFTR. Login to comment
144 BHK cells expressing mutants H139R, G149R, and R258G in the first transmembrane domain (TMD1)30 or mutants S945L and H949Y in TMD213 were treated with or without 3 µM CFcor-325 for 48 h. Whole cell SDS extracts were then subjected to immunoblot analysis. Login to comment
146 By contrast, CFcor-325 had little effect on mutants H139R or G149R. Login to comment
183 These include the substituted benzo[c]- quinolizinium compounds,39 thapsigargin,40 and curcumin.41 Drug rescue of ∆F508 CFTR with benzo[c]quinolizinium compounds, however, requires concentrations that are about 100-fold higher (250-500 µM) than that needed for CFcor-325, while rescue with thapsigargin and curcumin could not be repeated by other investigators.25,42,43 A possible explanation for the observation that curcumin treatment increased cAMP-stimulated iodide efflux in BHK cells expressing ∆F508 CFTR41 was that the compound can directly stimulate CFTR channels that were already present at the cell surface.44 We were unable to induce maturation of misprocessed CFTR mutants that had the mutations H139R or G149R in the first intracellular loop. Login to comment
207 (44) Berger, A. L.; Randak, C. O.; Ostedgaard, L. S.; Karp, P. H.; Vermeer, D. W.; Welsh, M. J. Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl-channel activity. J. Biol. Chem. 2005, 280, 5221-5226. in the first cytoplasmic loop (H139R or G149R) prevents the establishment of these interactions. Login to comment
24 Wild-type, ∆F508, H139R, G149R, R258G, S945L, and H949Y CFTR cDNAs were inserted into the pcDNA3 (Invitrogen, Oakville, ON) vector as described previously.13,14 Wild-type and mutant G268V P-gp cDNAs were inserted into the pMT21 vector (Genetics Institute) as described previously.15 Baby hamster kidney (BHK) cells stably expressing CFTR or P-gp were generated by cotransfection with cDNA and pWL-neo (Stratagene, Cedar Creek, TX). Login to comment
130 (C) BHK cells expressing misprocessed CFTR mutants H139R, G149R, R258G, S945L, H949Y, or wild-type CFTR were incubated for 48 h with (+) or without (-) 3 µM CFcor-325. Whole cell extracts were subjected to immunoblot analysis with a rabbit polyclonal antibody against CFTR. Login to comment
142 BHK cells expressing mutants H139R, G149R, and R258G in the first transmembrane domain (TMD1)30 or mutants S945L and H949Y in TMD213 were treated with or without 3 µM CFcor-325 for 48 h. Whole cell SDS extracts were then subjected to immunoblot analysis. Login to comment
181 These include the substituted benzo[c]- quinolizinium compounds,39 thapsigargin,40 and curcumin.41 Drug rescue of ∆F508 CFTR with benzo[c]quinolizinium compounds, however, requires concentrations that are about 100-fold higher (250-500 µM) than that needed for CFcor-325, while rescue with thapsigargin and curcumin could not be repeated by other investigators.25,42,43 A possible explanation for the observation that curcumin treatment increased cAMP-stimulated iodide efflux in BHK cells expressing ∆F508 CFTR41 was that the compound can directly stimulate CFTR channels that were already present at the cell surface.44 We were unable to induce maturation of misprocessed CFTR mutants that had the mutations H139R or G149R in the first intracellular loop. Login to comment
205 (44) Berger, A. L.; Randak, C. O.; Ostedgaard, L. S.; Karp, P. H.; Vermeer, D. W.; Welsh, M. J. Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity. J. Biol. Chem. 2005, 280, 5221-5226. in the first cytoplasmic loop (H139R or G149R) prevents the establishment of these interactions. Login to comment

PMID: 20837481 [PubMed] Pagant S et al: "Intragenic suppressing mutations correct the folding and intracellular traffic of misfolded mutants of Yor1p, a eukaryotic drug transporter."

No. Sentence Comment

84 We selected two mutations (G149R, located at the start of ICL1, and L1065P, located in ICL4 and predicted to participate directly in the NBD1-ICL4 interface) and introduced the equivalent mutations into Yor1p (Fig. 1A): Yor1p-G278R and Yor1p-I1084P, respectively. Login to comment

PMID: 22678879 [PubMed] El-Seedy A et al: "CFTR mutation combinations producing frequent complex alleles with different clinical and functional outcomes."

No. Sentence Comment

2 To elucidate the clinical significance of complex alleles involving p.Gly149Arg, p.Asp443Tyr, p.Gly576Ala, and p.Arg668Cys, we performed a collaborative genotype-phenotype correlation study, collected epidemiological data, and investigated structure-function relationships for single and natural complex mutants, p.[Gly576Ala;Arg668Cys], p.[Gly149Arg; Gly576Ala;Arg668Cys], and p.[Asp443Tyr;Gly576Ala; Arg668Cys]. Login to comment
3 Among 153 patients carrying at least one of these mutations, only three had classical CF and all carried p.Gly149Arg in the triple mutant. Login to comment
4 Sixty-four had isolated infertility and seven were healthy individuals with a severe mutation in trans, but none had p.Gly149Arg. Login to comment
5 Functional studies performed on all single and natural complex mutants showed that (1) p.Gly149Arg results in a severe misprocessing defect; (2) p.Asp443Tyr moderately alters CFTR maturation; and (3) p.Gly576Ala, a known splicing mutant, and p.Arg668Cys mildly alter CFTR chloride conductance. Login to comment
6 Overall, the results consistently show the contribution of p.Gly149Arg to the CF phenotype, and suggest that p.[Arg668Cys], p.[Gly576Ala;Arg668Cys], and p.[Asp443Tyr;Gly576Ala;Arg668Cys] are associated with CFTR-related disorders. Login to comment
21 These C 2012 WILEY PERIODICALS, INC. mutations have been further described in isolation, in association within complex alleles, and together with c.1327G>T, p.Asp443Tyr (D443Y) or c.445G>A, p.Gly149Arg (G149R) as triple mutants, notably in infertile patients with a congenital bilateral absence of the vas deferens (CBAVD) but also in patients with CF [Abramowicz et al., 2000; Bienvenu et al., 1997; Chillon et al., 1995a; Costes et al., 1995; Mercier et al., 1995; Pignatti et al., 1995; Ratbi et al., 2007; CFMD]. Login to comment
24 We thus implemented a collaborative study through the FrenchCFLaboratoryNetworktocollectallpatientsandindividuals carrying p.Asp443Tyr, p.Gly576Ala, p.Arg668Cys, and p.Gly149Arg, either in isolation or in complex alleles, and gathered epidemiological data on these mutations from the general population of France. Login to comment
26 Materials and Methods Patients and Healthy Individuals Patients and healthy individuals known to the French CF Laboratory Network before 1st January 2009, who were heterozygous for the p.Asp443Tyr, p.Gly576Ala, p.Arg668Cys, and p.Gly149Arg mutations, either in isolation or in a complex allele, were included. Login to comment
31 Epidemiological Study in the French General Population The allelic prevalences of the p.Asp443Tyr, p.Gly576Ala, p.Arg668Cys, and p.Gly149Arg mutations, either in isolation or in a complex allele, were determined by allele counting in a sample of healthy adult individuals from the French general population. Login to comment
44 Specific substitutions observed either in isolation (p.Gly149Arg, p.Asp443Tyr, p.Gly576Ala, and p.Arg668Cys) or in different combinations in patients were introduced into the WT CFTR plasmid using the Gene tailor site-directed mutagenesis kit (Invitrogen) and the designed primers (available upon request), in accordance with the manufacturer`s protocol (Fig. 1). Login to comment
91 Results Phenotype of Patients Carrying p.Asp443Tyr, p.Gly576Ala, p.Arg668Cys, and/or p.Gly149Arg in Various Combinations A total of 153 patients and healthy individuals carrying at least one of the alleles p.Asp443Tyr, p.Gly576Ala, p.Arg668Cys, and/or p.Gly149Arg, either in isolation or in a complex allele, were identified (Table 1). Login to comment
96 of patients Main diagnosis Additional information Age at diagnosis Sweat test (Cl-,mmol/L) Allele 1 Allele 2 2 CF P, PI 3 m1/2, 5 m NA p.[Gly149Arg;Gly576Ala;Arg668Cys] p.Phe508del 1 CF P, PI 6 y 92 p.[Gly149Arg;Gly576Ala;Arg668Cys] p.Phe508del 4 CF? Login to comment
110 The three classical CF patients carried the p.[Gly149Arg;Gly576Ala;Arg668Cys] complex allele in combination with a severe CF mutation in the other allele. Login to comment
111 In contrast to the other mutations, no genotypes involving p.Gly149Arg and a severe CF mutation in trans were found in any other patient with mild disease or in any of the healthy individuals. Login to comment
112 This raised the hypothesis that the major deleterious effect of the complex allele was attributable to p.Gly149Arg. Login to comment
124 Of the subset of 791 individuals who had undergone complete scanning of the coding regions, none were found to carry p.Gly149Arg (allelic frequency <0.20%). Login to comment
125 Processing of CFTR Mutants To evaluate the contribution of each mutation to the phenotype, we first studied the maturation of CFTR in HeLa cells that had been transiently transfected with cDNA encoding the WT and mutated CFTR proteins p.Gly149Arg, p.Asp443Tyr, p.Gly576Ala, and p.Arg668Cys in different combinations. Login to comment
136 C: Western blot analysis of the CFTR expression: 1, p.Phe508del; 2, p.[Gly149Arg;Gly576Ala;Arg668Cys]; 3, p.Gly149Arg; 4, WT. Login to comment
144 [Gly149Arg;Gly576Ala;Arg668Cys]proteins, whichwasindicativeofablockadeintheERcompartment(Fig.2C). Login to comment
149 In contrast, the p.Gly149Arg and p.[Gly149Arg;Gly576Ala;Arg668Cys] mutants exhibited no cell surface staining but did exhibit intense perinuclear staining (Figs. 3H and 3I). Login to comment
150 These experiments showed that p.Gly149Arg proteins were restricted to intracellular compartments, thus confirming the presence of a processing defect. Login to comment
151 Functional Analysis of Chloride Channel Function in CFTR Mutants To determine the impact of p.Gly149Arg, p.Asp443Tyr, p.Gly576Ala, and p.Arg668Cys in single, double, or triple mutants on CFTR chloride channel function, we expressed full-length WT and mutant proteins in HeLa cells, and measured chloride channel activity using single-cell fluorescence imaging and the potential-sensitive probe DiSBAC2(3)(Molecular Probes). Login to comment
158 In contrast, Cl- channel conductance was not detected in the cells transfected with p.Gly149Arg or p.[Gly149Arg;Gly576Ala;Arg668Cys]. Login to comment
160 Discussion In the present study, we investigated genotype-phenotype correlations and the in vitro consequences of CFTR mutations: four in isolation (i.e., p.Gly149Arg, p.Asp443Tyr, p.Gly576Ala, and p.Arg668Cys) and three complex alleles observed in patients or healthy individuals (i.e., p.[Gly576Ala;Arg668Cys], p.[Asp443Tyr;Gly576Ala;Arg668Cys], and the rarer p.[Gly149Arg; Gly576Ala;Arg668Cys]). Login to comment
166 Mutants (G) p.Phe508del, (H) p.Gly149Arg, (I) p.[Gly149Arg;Gly576Ala;Arg668Cys] were not targeted to the plasma membrane. Login to comment
170 Classification of Mutants with Regard to Clinical and Functional Data Classical CF was only observed in patients carrying p.Gly149Arg within the context of the complex allele p.[Gly 149Arg;Gly576Ala;Arg668Cys] in trans with a severe CF mutation. Login to comment
173 In contrast, genotypes combining mutants other than p.Gly149Arg, namely p.Arg668Cys, p.[Gly576Ala;Arg668Cys], and p.[Asp443Tyr;Gly576Ala;Arg668Cys], in trans with a CF mutation, were not observed in patients with classical CF, although they were observed in patients with moderate phenotypes, in particular CBAVD. Login to comment
178 This was corroborated by the observation that additional, different mutations occurred on this haplotype (p.Asp443Tyr, p.Gly149Arg, and p.Ser519Gly, the latter being observed only once in the sample from the general population). Login to comment
179 These results have substantial implications for diagnostic and genetic counseling, as they classify p.[Gly149Arg;Gly576Ala;Arg668Cys] or p.Gly149Arg (even if no CF patient was detected with only this mutation) as a CF-causing mutation, and p.Arg668Cys, p.[Gly576Ala;Arg668Cys], and p.[Asp443Tyr;Gly576Ala;Arg668Cys] as CFTR-RD mutations. Login to comment
180 Therefore, CF carrier testing in relatives and prenatal diagnosis should be offered or discussed only when p.Gly149Arg is present. Login to comment
191 D: HeLa cells transfected with WT CFTR as positive control, p.F508del as a negative control, and CFTR mutants as p.[Gly576Arg;Arg668Cys], [p.Asp443Tyr;Gly576Ala;Arg668Cys], p.[Gly149Arg; Gly576Arg;Arg668Cys] and p.Gly149Arg. Login to comment
196 In addition to clinical data, the present study provides molecular and functional evidence that the CFTR p.Gly149Arg mutation should be classified as a misprocessing, class II mutation [Welsh and Smith, 1993]. Login to comment
200 Interestingly, p.Gly149Arg is located in the first intracellular loop of MSD1,andwethereforehypothesizethatp.Gly149Argcouldmodify the interaction between MSD1 and NBD1, thus leading to a severe class II defect. Login to comment

PMID: 15463906 [PubMed] Dugueperoux I et al: "Cystic fibrosis at the Reunion Island (France): spectrum of mutations and genotype-phenotype for the Y122X mutation."

No. Sentence Comment

77 G 1 (1.49) D993Y 1 (0.68) DeltaF508/ G551D 1 (1.49) G149R 1 (0.68) DeltaF508/1161delC 1 (1.49) G85E 1 (0.68) Y122X/3120 + 1G ! Login to comment
79 A 1 (1.49) G551D 1 (0.68) G149R/993del5 1 (1.49) TOTAL 146 TOTAL 67 Frequencies given in this table are based on the 146 CF chromosomes with an identified CFTR mutation (detection rate of 83%). Login to comment

PMID: 10923036 [PubMed] Claustres M et al: "Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France."

No. Sentence Comment

105 d G149R, S489X, S492F, S549R, 1898+1G>A, 2622+1G>A, G970R, R1066H, W1204X, 3850-1G>A, Q1313X. Login to comment

PMID: 9305991 [PubMed] Seibert FS et al: "Disease-associated mutations in cytoplasmic loops 1 and 2 of cystic fibrosis transmembrane conductance regulator impede processing or opening of the channel."

No. Sentence Comment

107 The remaining amino acid substitutions significantly decreased the yield of band C, with relative amounts of "vector only" (background) < G149R-CFTR < H139R-CFTR < R258G-CFTR < D192G-CFTR , wild-type CFTR (Figure 2, bottom). Login to comment
120 In accordance with reduced levels of processing, the H139R, G149R, D192G, and R258G mutations significantly decreased the anion translocation capability of CFTR, whereas the properly processed I148T, I175V, and R297Q variants allowed iodide movement comparable to that of wild type. Login to comment
153 When reconstructed in heterologous expression systems, four of the amino acid substitutions (H139R, G149R, D192G, and R258G) inhibited maturation and transport of CFTR to the cell surface, so that the protein cannot carry out its regular functions at that location. Login to comment

PMID: 8530001 [PubMed] Ferec C et al: "Neonatal screening for cystic fibrosis: result of a pilot study using both immunoreactive trypsinogen and cystic fibrosis gene mutation analyses."

No. Sentence Comment

58 Sweat test values are borderline for one neonate (60 mmol/l, genotype G551D/R553G) and normal for two neonates of genotype AF508/G149R and AF508/R1070 W. Login to comment
63 This scanning of the gene permitted the identification of compound heterozygosity in two children (AF508/R1070 W, AF508/G149R; see Table 1). Login to comment
82 {17bi DI507 [ Y569X W846X 2789+5G->A ,' $492F i ] i I G551D 2622+1 G->A Y1092X 1717-1 G->A E827X A1067T G542X 2183 AA->G R1066H R560K 2184 ins A 3320,ins 5 R553G R1070W 1806 del A & 4005+1G->A W1282X ] i "- Exons Fig.2 Distribution of the different mutations (except AF508) of the CFTR gene in Brittany Table 1 Mutations and genotypes in newborns Genotypes of newborns Number Sweat test AF508/AF508 7 + > 90 AF508/1806 del A 1 + > 90 R553G/G551D 1 Borderline (60) AF508/G551D 1 + > 90 AF508/R1070W 1 40 AF508/G542X 1 + > 90 AF508/G149R 1 45 Total 13 Mutations found in heterozygote newborns AF508 31 R560K 1 1078 del T 1 G544S l G542X 1 V317A 1 R347H 1 V322A 1 Total 38 gene. Login to comment
123 R553G is described for the first time in this paper; Rl070 W and G149R are rare alleles and have been described in an analysis by the CF Genetic Consortium on one or two chromosomes (personal communication). Login to comment

PMID: 7739684 [PubMed] Chillon M et al: "Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens."

No. Sentence Comment

74 OF PATIENTS POLYT GENOTYPE† ⌬F508/R668C ⌬F508/D1152H ⌬F508/D1270N ⌬F508/R75L ⌬F508/R117H ⌬F508/L206W ⌬F508/R258G ⌬F508/S1235R ⌬F508/R347H ⌬F508/R347H R117H/G1349D R117H/712-1G→T G149R/R668C R347H/R1066H R553X/R668C R1070W/2869insG ⌬F508/- G542X/- W1282X/- R334W/- K1060T/- R1162X/- N1303K/- A800G/- ⌬F508/- ⌬F508/- ⌬F508/- ⌬E115/- R117H/- R347H/- G542X/- R553X/- 1677delTA/- 2184delA/- 2789ϩ5G→Α/- S1235R/- W1282X/- -/- -/- -/- -/- 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 22 4 3 1 1 1 1 1 7 1 1 1 1 2 1 1 1 1 1 1 1 3 3 1 19 9T/7T 9T/7T 9T/7T 9T/7T 9T/7T 9T/9T 9T/7T 9T/7T 9T/7T 9T/9T 7T/7T 7T/9T 9T/7T 9T/7T 7T/7T 7T/7T 9T/5T 9T/5T 7T/5T 7T/5T 7T/5T 7T/5T 9T/5T 5T/5T 9T/7T 9T/9T 7T/7T 7T/7T 7T/7T 9T/7T 9T/7T 7T/7T 7T/7T 7T/7T 7T/7T 7T/9T 7T/7T 9T/5T 7T/5T 5T/5T 7T/7T -/- 3 7T/9T *Data were obtained from the Spanish population analyzed in this study. Login to comment

PMID: 7529962 [PubMed] Mercier B et al: "Is congenital bilateral absence of vas deferens a primary form of cystic fibrosis? Analyses of the CFTR gene in 67 patients."

No. Sentence Comment

7 We have identified four novel missense mutations (A800G, G149R, R258G, and E193K). Login to comment
65 In addition, we identified the following missense mutations: four R668C, one A800G, one (G628R + S1235R, borne on the same chromosome), one (R74W + D1270N, borne on the same chromosome), six R117H, one F1052V, one R117C, one S1235R, one G149R, one R258G, two R347H, one R1066H, one R75L, and one E193K. Login to comment
77 of Patients Genotypea 1 AF508 + (G628R + S1235R) 1 AF508 + (R74W + D1270N) 2 AF508 + R668C 4 AF508 + R117H 1 AF508 + R258G 1 AF508 + R75L 1 E193K + N1303K 1 R347H + R1066H 1 R117C + W1282X 1 R553X + R668C 1 G149R + R668C 1 R117H+R117H 18 AF508/unidentified 4 W1282X/unidentified 1 G542X/unidentified 1 N1303K/unidentified 1 S1235R/unidentified 1 R347H/unidentified 1 A800G/unidentified 1 F1052V/unidentified 23 unidentified/unidentified a In parentheses are the two mutations located on the same haplotype. Login to comment
84 (ii) The second change, situated in exon 4, is G-o.A at position 577 and corresponds to the substitution of a glycine for an arginine (G149R). Login to comment
92 For all four of these new mutations, a segregation analysis was performed in each family, allowing us to show that G149R, R258G, and E193K were carried by a particular allele and that these mutations were not de novo mutations. Login to comment
107 C T A G G T A T G A A G-A T A G T T T A G ATC C C T C A a G C->G A A A C T T G E193K T C A C A T T G-A G A A T a C A ASOOG Figure 2 Autoradiographs showing nucleotide sequence of portions of exons 5, 13, and 4 of CFTR and demonstrating the mutations E193K, A800G, and G149R, respectively. Login to comment

PMID: 17823699 [PubMed] Pieri Pde C et al: "Novel CFTR missense mutations in Brazilian patients with congenital absence of vas deferens: counseling issues."

No. Sentence Comment

58 A different mutation (G149R) at the same position was previously reported in a CBAVD patient11 but was not found in normal individuals nor in CF patients tested, placing the G149R in the category of Class V mutation usually associated to the CBAVD phenotype.11 The G to W substitution described here is probably even milder than G to R, once glycine and tryptophan are both not polar amino acids. Login to comment