ABCMdb

ABCC7 p.Arg297Gln

None has been submitted yet.

Publications

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

No. Sentence Comment

199 R297Q, which shows a similar level of maturation as the wild-type CFTR, showed CFTR-like channel activity. 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: 11168024 [PubMed] Scotet V et al: "Prevalence of CFTR mutations in hypertrypsinaemia detected through neonatal screening for cystic fibrosis."

No. Sentence Comment

11 Variability of mutations detected in carriers was greater than in CF children (21 mutations versus 10) and a high proportion of mild mutations or variants (A349V, R297Q, R347H, V317A, G544S, R553G, etc) was observed in carriers. Login to comment
74 We noted, among heterozygous children, a high proportion of mild mutations (R297Q, R347H, M348K, A349V, G544S) or for which the pathogenicity is yet impossible to determine (V317A, V322A, R553G). Login to comment
89 Molecular abnormalities detected in exons 7, 10 and 11 of the CFTR gene in a control population and in the affected and heterozygous children identified by the neonatal screening between 1992 and 1998 in Brittany, France ContributorsAlleles in the controlAlleles in affectedMolecular abnormalities Alleles in carrierExon Type children populationchildren No % No % No % Disease causing mutations Y301C 7 Mild 1 0.47 Constantinou-Deltas CD et al.* 7 Mild 1 1.03 9 4.22 Cremonesi L et al. (38)R347H Audre´zet MP et al. (39)0.471Mild7M348K 7 MildA349V 1 0.47 Audre´zet MP et al. (30) Fe´rec C et al. (29)0.471Mild10S492F 0.942 This studyMild11G544S 11 MildI556V 1 0.47 Ghanem N et al.* R560K 11 Mild 1 0.47 Fe´rec C et al. (29) 1078delT 7 Severe 2 2.06 5 2.35 Claustres M et al. (40) Fe´rec C et al. (29)0.471Severe71221delCT DF508 10 Severe 81 83.51 170 79.81 11 2.6 Kerem B et al. (12) DI507 Schwarz M et al. (41)0.471Severe10 11 Severe1717-1 GA 1 1.03 3 1.41 Kerem B et al. (42) Scotet V et al. (28)1.0311806delA 11 Severe Kerem B et al. (42)1.8743.09G542X 11 Severe 3 5.16 5 2.35 Cutting GR et al. (43)G551D 11 Severe 5 Cutting GR et al. (43)1 0.471.03R553X 11 Severe 1 Non-disease causing mutations R297Q 7 1 1.03 1 0.47 Graham CA et al.* 0.942 This study7V317A V322A 7 1 0.47 This study 11 1 1.03 1 0.47 Scotet V et al. (28)R553G 11R553Q 1 0.47 Dork T et al. (44) 97 100 213 100 422 100 * From Cystic Fibrosis Genetic Analysis Consortium (http://www.genet.sickkids.on.ca) An excess of heterozygotes carrier of the most frequent mutation (DF508) among neonates with hypertrypsinaemia has been reported (23, 24). Login to comment

PMID: 11242048 [PubMed] Choi JY et al: "Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis."

No. Sentence Comment

186 letters to nature 96 NATURE |VOL 410 |1 MARCH 2001 |www.nature.com HCO3 -/Cl- transportratio 0 0.25 0.50 0.75 1.00 WT I148T G178R R297Q G551D H620Q G970R A1067T G1244E S1255P G1349D E193K G551S A800G H949Y R1070Q Pancreatic insufficient Pancreatic sufficientD648V N CI148T G178R E193K R297Q R117H A1067T R1070Q G1244E S1255P G1349D NBD2 RD H949Y G970R CL4CL3CL2CL1 NBD1 G551D G551S H620Q D648V A800G Figure 3 The HCO3:Cl-transport ratio of CFTR mutants associated with CF. Login to comment

PMID: 11354633 [PubMed] Tzetis M et al: "CFTR gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease."

No. Sentence Comment

47 Of the 17 mutations in the patients, 9 (Y301C, I148T, R297Q, S1235R, T896I, S977F, L997F, F1052 V, A120T) have been listed by the Cystic Fibrosis Genetic Analysis Consortium (see website: http://www.cf.genet.sickkids. Login to comment
60 of CFTR gene IVS8-(T)n IVS8-(TG)m M470 V tested cases mutationa Asthma 20 1 L997F, T338Mb 9/7 10/12 M/V 1 Y301C 7/7 11/11 V/V 1 M1Rb, V11Ib 7/7 12/10 M/M 1 I148T/- 9/9 10/10 M/V 1 L997F/- 9/9 11/9 M/V 1 R297Q/- 5/5 13/11 M/M 1 R297Q/- 7/7 11/11 V/V 1 R75Q/- 7/7 11/11 V/V 1 A120T/ 5/7 11/11 V/V 1 -/- 7/7 11/12 M/V 1 -/- 7/9 11/11 M/M 2 -/- 7/7 12/10 M/V 7 -/- 7/7 11/11 V/V DB 19 1 F508del, I1027T 9/9 10/10 M/M 1 D565G, R668C 7/7 11/11 M/V 1 T896I/- 7/7 11/10 M/V 1 I148T/- 7/9 11/10 M/V 1 F508del/S977F 5/9 12/10 M/V 1 -/- 7/9 12/10 V/V 1 -/- 7/9 10/10 M/V 1 -/- 7/7 11/12 M/M 2 -/- 7/7 11/10 1 M/V, 1 V/V 2 -/- 7/7 12/10 1 V/V, 1 M/M 3 -/- 7/9 11/10 1 M/M, 2 V/V 4 -/- 7/7 11/11 1 V/V, 3 M/V COPD 12 1 F1052 V/- 7/7 11/10 M/V 1 S1235R/- 7/9 12/10 M/M 1 -/- 5/5 11/12 M/V 1 -/- 7/9 10/10 M/M 2 -/- 7/9 11/10 1 M/M,1 M/V 3 -/- 7/7 11/10 M/V 3 -/- 7/7 11/11 1 M/V, 2 M/M Controls 52 1 F508del/- 7/9 10/10 M/M 1 F1052 V/- 5/7 10/11 M/V 1 F1052 V/- 7/7 11/11 M/M 1 R668C, D565G/- 7/7 11/11 M/M 1 R688C, D565G/- 7/7 11/10 M/V 1 R75Q/- 7/7 11/11 V/V 1 R297Q/- 7/7 11/10 M/V 1 L997F/- 7/9 10/10 M/V 1 -/- 7/7 10/10 M/V 1 -/- 7/9 10/10 M/M 1 -/- 7/9 12/10 M/M 4 -/- 7/9 11/10 1 M/M, 1 V/V, M/V 15 -/- 7/7 11/10 13 M/V, 2 V/V 22 -/- 7/7 11/11 18 V/V, 3 M/V, 1 M/M been found that affect the same codon, of which M1 K affects the same nucleotide (T>A) (Cystic Fibrosis Genetic Analysis Consortium website). Login to comment
72 The proportion of CFTR alleles in each group is expressed as c/d (e), where c indicates the number of alleles with the genotype indicated at left, d indicates the number of total alleles examined in each group and e represents the percentage aMutation name according to the Cystic Fibrosis Genetic Analysis Consortium bNovel mutations, reported for the first time in this study Mutationa Control Pulmonary disease patients Greek CF population patients (PS; PI) (n=52) Asthma DB COPD (n=426) (n=20) (n=19) (n=12) R75Q (356 G/A, exon 3) 1 (0.96%) 1 (2.5%) - - 1 (0.1%) R668C (2134 C/T, exon 13) 2 (1.9%) - 1 (2.6%) - 1 (0.1%) L997F (3123 G>C, exon 17a) 1 (0.96%) 2 (5%) - - - F508del 1 (0.96%) - 2 (5.3%) - 465 (54.6%) D565G (A>G at 1825, exon 12) 2 (1.9%) - 1 (2.6%) - 1 (0.1%) F1052 V (T>G at 3286, exon 17b) 2 (1.9%) - - 1 (4.2%) 1 (0.1%) R297Q (G>A at 1022, exon 7) 1 (0.96%) 2 (5%) - - - Y301C (A>G at 1034, exon 7) - 1 (2.5%) - - - I148T (T>C at 575, exon 4) - 2 (5%) - - 1 (0.1%) T388Mb (C>T at 1295, exon 8) - 1 (2.5%) - - - M1Rb (T>G at 134, exon 1) - 1 (2.5%) - - - V11Ib (G>A at 163, exon 1) - 1 (2.5%) - - - I1027T (3212 T/C, exon 17a) - - 1 (2.6%) - 1 (0.1%) T896I (C>T at 2819, exon 15) - - 1 (2.6%) - - S977F (C>T at 3062, exon 16) - - 1 (2.6%) - - A120T (G>A at 490, exon 4) - 1 (2.5%) - - - S1235R (T>G at 3837, exon 19) - - - 1 (4.2%) - Table 3 Frequency of M470 and (TG)mTn alleles in pulmonary disease patients and controls (DB disseminated bronchiectasis, COPD chronic obstructive pulmonary disease, n number of cases, ND not detected) Clinical status Allele M470 TG11/T7 TG10/T7 TG12/T7 TG10/T9 TG11/T5 TG12/T5 TG13/T5 Asthmaa (n=20) 13 (32.5%) 23 (57.5%) 3 (7.5%) 5 (12.5%) 3 (7.5%) 2 (5%) ND 1 (2.5%) DB (n=19) 17 (44.7) 18 (47.4%) 6 (15.8%) 4 (10.5%) 9 (23.7%) ND 1 (2.6%) ND COPD (n=12) 17 (70.8) 12 (50%) 5 (20.8%) 1 (4.2%) 4 (16.7%) 1 (4.2%) 1 (4.2%) ND Controls (n=52) 37 (35.5%) 71 (68.%) 23 (22.1%) 1 (0.96%) 6 (5.8%) 1 (0.96%) ND ND aAlleles TG11/T9 (2) and TG9/T9 (1) also detected alleles, P<0.01) were both found more frequently in patients with COPD. Login to comment
75 Of them, one was homozygous for the IVS8-5T allele and also carried mutation R297Q, and another carrier of mutation A120T was heterozygous for the IVS8-5T allele. Login to comment
76 The phase of the IVS8-5T allele regarding the A120T mutation is not known, but the patient with the R297Q mutation could be considered a CF compound heterozygote. Login to comment
102 Two asthma patients (genotypes: R297Q/-, A120T/-) carried haplotypes TG13/T5/M470, TG11/T5/M470 and TG11/T5/V470, which have been found almost exclusively among CBAVD patients and not among those with normal CFTR genes (Costes et al. 1995). Login to comment
105 In the case of the asthma patient, the milder mutation R297Q could, in association with the particular haplotype, produce the phenotype of asthma. Login to comment

PMID: 11788091 [PubMed] Ravnik-Glavac M et al: "Involvement of CFTR gene alterations in obstructive and nonobstructive infertility in men."

No. Sentence Comment

56 The third, R297Q, was originally reported in patients with the classical disease (Cutting et al., 1992), but it has more recently been described in healthy persons who have also inherited a known pathological CF mutation, making it more likely that R297Q is a polymorphismrather than a deleterious mutation (Dorval et al., 1995). Login to comment
58 R297Q and S1235R were each detected as a single allele in men with oligoas- thenoteratozoospermiaand oligozoospermia, respectively. Login to comment
66 DETECTED NUCLEOTIDE ALTERATIONS IN CFTR GENES AND THEIR FREQUENCY IN MEN WITH INFERTILITY AND SUBFERTILITY AND IN CONTROL POPULATION CFTR Nucleotide Amino acid Type of Azoo Oligo OAT CBAVD Controls gene change change change (n 5 160) (n 5 100) (n 5 140) (n 5 14) (n 5 190) Ex 3 356G ® A R75Q P 2 0 1 0 1 Int 3 405 1 35C ® T / V 1 0 0 0 0 405 1 46G ® T / P 4 0 3 0 1 Ex 4 519T ® A L129L V 0 1 0 0 0 549C ® T H139H V 0 1 0 0 0 Ex 7 1022G ® A R297Q M 0 0 1 0 0 Int 8 IVS8-5T / P 8 4 10 3 8 Ex 10 1652del3 DF508 M 1 2 0 2 3 Int17a 3272-93T ® Ca / P 6 2 4 0 4 Ex17b 3417A ® T T1095T P 2 0 1 0 3 Ex 19 3837T ® G S1235R M 0 1 0 0 0 Ex 20 4002A ® G P1290P P 6 2 4 0 4 Ex 21 4029A ® G T1299T P 0 0 1 0 1 Abbreviations: P, Polymorphism; Azoo, azoospermia; V, variation; Oligo, oligozoospermia; M, pathogenic mutation; OAT, oligoasthenoteratozoospermia CBAVD, congenital bilateral absence of the vas deferens; Ex, exon; Int, intron. Login to comment

PMID: 12007216 [PubMed] Bobadilla JL et al: "Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening."

No. Sentence Comment

109 Mutational Arrays, Detection Rates and Methods by Region* Estimated Projected detection of Number of Number of Country/ allele two CFTR mutations chromosomes Region Mutation array detectiona mutationsb includedc (max/min)d Reference Europe Albania ∆F508 (72.4%) C276X (0.7%) 74.5 55.5 4 270/146 CFGAC [1994]; Macek et al. G85E (0.7%) R1070Q (0.7%) [2002] Austria ∆F508 (62.9%) 457TAT→G (1.2%) 76.6 58.7 11 1516/580 Estiville et al. [1997]; Dörk et al. (total) G542X (3.3%) 2183AA→G (0.7%) [2000]; Macek et al. [2002] CFTRdele2,3 (2.1%) N1303K (0.6%) R1162X (1.9%) I148T (0.5%) R553X (1.7%) R117H (0.5%) G551D (1.2%) Austria ∆F508 (74.6%) 2183AA→G (2.4%) 95.3 90.8 8 126 Stuhrmann et al. [1997] (tyrol) R1162X (8.7%) G551D (1.6%) G542X (2.4%) R347P (1.6%) 2789+5G→A (2.4%) Q39X (1.6%) Belarus ∆F508 (61.2%) R553X (0.5%) 75.2 56.6 9 278/188 Dörk et al. [2000]; Macek et al. G542X (4.5%) R334W (0.5%) [2002] CFTRdele2,3 (3.3%) R347P (0.5%) N1303K (3.2%) S549N (0.5%) W1282X (1.0%) Belgium ∆F508 (75.1%) 622-1A→C (0.5%) 100.0 100.0 27 1504/522 Cuppens et al. [1993]; Mercier et G542X (3.5%) G458V (0.5%) al. [1993]; CFGAC [1994]; N1303K (2.7%) 1898+G→C (0.5%) Estivill et al.[1997] R553X (1.7%) G970R (0.5%) 1717-1G→A (1.6%) 4218insT (0.5%) E60X (1.6%) 394delTT (0.5%) W1282X (1.4%) K830X (0.5%) 2183A→G+2184delA (1.2%) E822K (0.5%) W401X (1.0%) 3272-1G→A (0.5%) A455E (1.0%) S1161R (0.5%) 3272-26A→G (1.0%) R1162X (0.5%) S1251N (1.0%) 3750delAG (0.5%) S1235R (0.8%) S1255P (0.5%) ∆I507 (0.6%) Bulgaria ∆F508 (63.6%) R75Q (1.0%) 93.0 86.5 21 948/432 Angelicheva et al. [1997]; (total) N1303K (5.6%) 2183AA→G (0.9%) Estivill et al. [1997]; Macek G542X (3.9%) G1244V+S912L (0.9%) et al. [2002] R347P (2.2%) G85E (0.9%) 1677delTA (2.1%) 2184insA (0.9%) R1070Q (1.8%) L88X+G1069R (0.8%) Q220X (1.2%) 2789+5G→A (0.8%) 3849+10KbC→T (1.1%) G1244E (0.8%) W1282X (1.0%) 1717-1G→A (0.8%) 2176insC (1.0%) Y919C (0.7%) G1069R (1.0%) WORLDWIDEANALYSISOFCFTRMUTATIONS581 Bulgaria 1) DF508 4) 1677delTA - - 6 13 Angelicheva et al. [1997] (ethnic 2) R347P 5) Q493R Turks) 3) G542X 6) L571S - - 1 30 Angelicheva et al. [1997] Bulgaria 1) DF508 (100.0%) (Gypsy) Croatia ∆F508 (64.5%) G551D (1.1%) 72.5 52.6 5 276 Macek et al. [2002] G542X (3.3%) 3849+10KbC→T (0.7%) N1303K (2.9%) Czech ∆F508 (70.0%) 1898+1G→T (2.0%) 89.6 80.3 10 2196/628 CFGAC [1994]; Estiville et al. Republic CFTRdele2,3 (5.5%) 2143delT (1.2%) [1997]; Dörk et al. [2000]; G551D (3.8%) R347P (0.8%) Macek et al. [2002] N1303K (2.9%) 3849+10KbC→T (0.6%) G542X (2.2%) W1282X (0.6%) Denmark ∆F508 (87.5%) G542X (0.7%) 92.3 85.2 6 1888/678 CFGAC [1994]; Schwartz et al. (excluding 394delTT (1.8%) 621+1G→T (0.6%) [1994]; Estiville et al. [1997] Faroe) N1303K (1.1%) 3659delC (0.6%) Estonia ∆F508 (51.7%) R117C (1.7%) 80.2 64.3 10 165/80 Estivill et al. [1997]; Klaassen et 394delTT (13.3%) E217G (1.7%) al. [1998]; Macek et al. S1235R (3.3%) R1066H (1.7%) [2002] 359insT (1.7%) 3659delC (1.7%) I1005R (1.7%) S1169X (1.7%) Finland ∆F508 (46.2%) G542X (1.9%) 78.8 62.1 4 132/52 CFGAC [1994]; Kere et al. 394delTT (28.8%) 3372delA (1.9%) [1994]; Estivill et al. [1997] France ∆F508 (67.7%) 2789+5G→T (0.79%) 79.7 63.6 12 17854/7420 Chevalier-Porst et al. [1994]; (total) G542X (2.94%) 2184delA+2183A→G (0.77%) Estivill et al. [1997]; Claustres et al. [2000]; Guilloud-Bataille N1303K (1.83%) G551D (0.74%) et al. [2000] 1717-1G→A (1.35%) 1078delT (0.63%) W1282X (0.91%) ∆I507 (0.62%) R553X (0.86%) Y122K (0.59%) France ∆F508 (75.8%) R297Q (0.8%) 98.7 97.4 18 599/365 Férec et al. [1992]; Scotet et al. (Brittany) 1078delT (4.0%) R347H (0.8%) [2000] G551D (3.6%) I1234V (0.8%) N1303K (3.0%) R553X (0.8%) R117H (1.7%) 2789+5G→A (0.8%) 3272-26A→G (1.3%) 4005+1G→A (0.7%) G542X (1.1%) 621+1G→T (0.6%) 1717-1G→A (1.0%) ∆I507 (0.6%) G1249R (0.8%) W846X (0.5%) France ∆F508 (70.0%) N1303K (0.8%) 90.4 81.7 16 250 Claustres et al. [1993] (southern) G542X (6.4%) 3737delA (0.8%) 1717-1G→A (1.6%) R1162X (0.8%) L206W (1.2%) Y1092X (0.8%) R334W (1.2%) S945L (0.8%) ∆I507 (1.2%) K710X (0.8%) 2184delA (1.2%) 1078delT (0.8%) R1158X (1.2%) Y122X (0.8%) (Continued) BOBADILLAETAL. Login to comment

PMID: 15097853 [PubMed] Casals T et al: "Different CFTR mutational spectrum in alcoholic and idiopathic chronic pancreatitis?"

No. Sentence Comment

63 Time Years BMI Alcohol Alcohol Time Years Tobacco Pancreatic Features Hepatobiliary Disease CFTR Genotype Sweat Test mmol/L FEV1/FVC % Predicted Male Fertility Alcoholic Chronic Pancreatitis (n = 15) 1 M/52 15 24.5 110g/d 27 yes AP, P, Ps, DM, PI Chronic hepatitisa F508del/S1235R 18 105/107 yes 2 M/72 15 23.4 85g/d 22 yes AP, P, C, PS no F508del/1716G/A 72 90/104 yes 3 M/53 10 21.9 135g/d 20 yes P, C, DM, PI no F508del/- 54 71/89 yes 4 M/64 18 20.7 250g/d 27 yes AP, P, C, Ps, DM, PI cirrhosis, lithiasis W1282X/- 68 71/78 unproved 5 M/44 13 22.0 95g/d 6 yes AP, P, C, Ps, DM, PI lithiasis R170C/- 16 105/111 yes 6 M/62 12 22.1 >60g/d >5 yes AP, P, C, Ps, DM, PS no R258G/- 82 73/82 yes 7 M/38 9 18.0 210g/d 15 yes AP, P, C, Ps, PS no M281T/- 62 132/126 yes 8 M/40 11 - >60g/d >5 yes AP, P, C, Ps, PS lithiasis R297Q/- 46 103/99 yes 9 M/42 2 21.4 150g/d 20 yes AP, P, C, Ps, PS no 1716G/A/- 19 93/102 yes 10 M/44 3 22.2 95g/d 22 yes AP, P, DM, PS no R668C/- 58 105/102 yes 11 M/59 6 21.8 90g/d 18 yes PS lithiasis L997F/- 85 69/84 nd 12 M/72 16 - >60g/d >5 no P, C, DM, PI lithiasis R1162L/- - - yes 13 M/35 8 21.0 90g/d 7 yes AP, P, C, PS no 5T-12TG-V470/- 13 106/114 unproved 14 M/60 14 28.0 80g/d 20 no AP, P, C, Ps, DM, PI no 5T-11TG/- 28 80/77 yes 15 M/65 12 24.4 100g/d 23 yes AP, P, C, DM, PS no 5T-11TG/ 40 86/110 yes Idiopathic Chronic Pancreatitis (n = 12) 16 M/21 5 - no - yes AP, P, PS no 1716G/A/R170H 40 normal yes 17 M/59 4 24.2 no - no PS chronic hepatitisb 1716G/A/- 40 146/128 yes 18 M/63 14 21.4 no - no DM, PI no 1716G/A/- 34 144/126 yes 19 M/70 18 19.9 no - yes AP, P, DM, PI chronic hepatitisa 1716G/A/- 60 36/47 yes 20 M/65 1 27.7 no - yes P, Ps, DM, PI no 1716G/A/- 38 79/78 yes 21 M/76 8 24.1 no - no AP, P, DM, PS no 1716G/A/- 60 81/109 yes 22 M/25 2 25.0 no - yes AP, P, PS no 1716G/A/- 48 94/86 nd 23 F/42 10 22.6 no - yes P, C, PS lithiasis P205S/- 72 111/109 - 24 F/81 21 34.6 no - no P, C, DM, PI lithiasis D443Y+G+R*/- 42 121/108 - 25 F/72 8 23.3 no - yes AP, C, PS no L997F/- 40 100/93 - 26 M/9 2 19.2 no - no AP, P, PS no 5T-11TG/- 30 101/110 nd 27 M/63 6 - no - no C, DM, PI cirrhosis 5T-11TG/- - - yes a C virus hepatitis. Login to comment

PMID: 15614862 [PubMed] D'Apice MR et al: "Segregation analysis in cystic fibrosis at-risk family demonstrates that the M348K CFTR mutation is a rare innocuous polymorphism."

No. Sentence Comment

46 This is similar to the situation for the R297Q mutation (Dorval et al., 1995). Login to comment

PMID: 16126774 [PubMed] Morea A et al: "Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility."

No. Sentence Comment

76 This test involved nine subjects from the infertile group, revealing the occurrence of the following rare mutations: E217G, T1054A, W356X, D443Y and 3667insTC in males and L997F and R297Q in females and 29 subjects from the control, in which we found: A1009T, D110Y, E826K, G1069R, G1130A, G194V, I556V, L320F, M348K, M82V, P1290T, R117C, R352W, R74W, S42F, S660T, S911R, S912L, T1086A, T582S, V920L and Y89C. Login to comment

PMID: 16778595 [PubMed] Sun W et al: "CFTR 5T variant has a low penetrance in females that is partially attributable to its haplotype."

No. Sentence Comment

123 Previous reports showed that individuals carrying the haplotype were symptomatic with pancreatic-sufficient CF16,24 (in trans to ⌬F508), CBAVD,16,36 or asthma22 (in trans to R297Q). Login to comment

PMID: 17003641 [PubMed] Keiles S et al: "Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis."

No. Sentence Comment

54 Patients With More Than 1 CFTR Mutation CFTR Mutation 1 CFTR Mutation 2 CFTR Mutation 3 No. of Patients deltaF508 5T 3 deltaF508 D1152H 1 deltaF508 deltaF508 1 deltaF508 F575Y 1 deltaF508 K598E 1 deltaF508 T164S 1 deltaF508 R74W D1270N 1 deltaF508 Q1476X 1 deltaF508 L997F 1 R553X D1152H 1 R553X G1069R 1 2789+5 G9A 2183 AA9G 1 3849+10kb C9T L1260P 1 711+3 A to G I1139V 1 1341+1 G9A G194R 5T 1 621+25 A9G 3500-19 C9T 1 R74W V855I 1 G542X R117H 1 G551D F311L 1 G576A R668C 2 K710X L997F 1 L997F L320V 1 G1069R 5T 1 1818+18 G9A 5T 1 F1074L 5T 1 F834L 5T 1 R74Q R297Q 1 R74Q R297Q 5T 1 R785Q 5T 1 R117H 5T 3 deltaF508 I1027T 1 Total patients 36 MutationsinboldfacewouldnothavebeendetectedbytheAmericanCollegeofObstetrics and Gynecology (ACOG)/American College of Medical Genetics (ACMG) mutation panel. Login to comment
71 Patients With 1 CFTR Mutation CFTR Mutation 1 No. of Patients 1717-1 G9A 1 2789+5 G9A 1 3849+10kb C9T 2 3849+45 G9A 1 621+3 A9G 2 A1364V 1 A349V 1 A455E 1 D1152H 1 D1445N 1 deltaF508 16 E217G 1 F1286C 1 F316L 1 G542X 1 G551D 1 I148T 1 I807M 1 L206W 1 L967S 2 L997F 2 P55S 1 Q179K 1 Q220X 1 R117H 3 R1453W 1 R297Q 1 R31C 1 R668C 2 S1235R 1 S573C 1 S945L 1 V562A 1 V754M 2 Y1092X 1 Total patients 58 MutationsinboldfacewouldnothavebeendetectedbytheACOG/ACMGmutationpanel. Login to comment

PMID: 17489851 [PubMed] Tzetis M et al: "Contribution of the CFTR gene, the pancreatic secretory trypsin inhibitor gene (SPINK1) and the cationic trypsinogen gene (PRSS1) to the etiology of recurrent pancreatitis."

No. Sentence Comment

93 a Additional mutations found in the controls: p.R1162L (1.66%), p.D565G (0.47%), p.A120T (0.47%) and 0.24% each for p.R297Q, p.L997F, p.E826K, p.I807M, p.S495Y and p.C491S. Login to comment

PMID: 18597042 [PubMed] Mornon JP et al: "Atomic model of human cystic fibrosis transmembrane conductance regulator: membrane-spanning domains and coupling interfaces."

No. Sentence Comment

262 In ICL2, the only missense mutation reported that was characterized at the functional level (R297Q) had little effect on the CFTR chloride channel activity [73]. Login to comment

PMID: 19812525 [PubMed] de Cid R et al: "Independent contribution of common CFTR variants to chronic pancreatitis."

No. Sentence Comment

74 To simplify, as previously mentioned, the 4 CFTR-related disorderYassociated mutations, 5T-12TG, L997F, R297Q, and D443Y-G576A-R668C, have been grouped together with the CF-causing mutations in front of other CFTR mutations without or unknown clinical relevance13 (Table 3). Login to comment
82 *Patients previously reported.12 † CF-causing mutations and mutations associated to CFTR-related disorders (5T-12TG, L997F, R297Q, and D443Y-G576A-R668C). Login to comment

PMID: 20416310 [PubMed] Ooi CY et al: "Genetic testing in pancreatitis."

No. Sentence Comment

53 Interpretation of Mutations Requires an Understanding of Their Functional Consequences Mutation group Reported mutations Complex allele: These mutations are recognized to occur on a single allele R117H ϩ T G576A ϩ R668C F508del ϩ I1027T Benign sequence alterations: These mutations have no known clinical consequence R74Q R297Q R74W 621 * 25 AϾG 3500-19 CϾT T164S C855I I1139V CFTR-related disorder associated: These mutations have been described in individuals with CF-like single organ disease (such as pancreatitis, sinopulmonary disease, or obstructive azoospermia), but do not fulfill the diagnostic criteria for CF 5T R117H D1270N L320V Q1352H 1818-18 GϾA S1235R CF causing F508del Q1476X R553X K710X G542X G551D F311L 2789-5 GϾA 2183AAϾG 711ϩ3 AϾG 3849ϩ10kb CϾT 1341ϩ1GϾA D1152Ha F1074La R553X Unknown clinical consequence F575Y L1260P G194R G1069R L997F K598E F834L R785Q To illustrate this point, mutations identified by extensive mutation testing in a cohort of patients with recurrent acute or chronic pancre- atitis14 are listed according to their clinical consequences (based on current consensus guidelines13 and functional and/or clinical reports; available: http://www.genet.sickkids.on.ca). Login to comment

PMID: 20846557 [PubMed] Sutton JM et al: "Total pancreatectomy and islet cell autotransplantation as a means of treating patients with genetically linked pancreatitis."

No. Sentence Comment

117 Patient demographics Descriptive statistics Data mean (SEM) Range Age, y 32 (3) 15-59 Weight, kg 73 (6) 39-127 Body mass index, kg/m2 24 (2) 15-35 Chronic pancreatitis, y 14 (2) 3-47 Sex Male, n = 8 Female, n = 8 Previous pancreatic operations Puestow, n =3 Whipple, n = 3 Genetic mutations and loci, n (%) CFTR 10 (62.5) R297Q 2 DF508 + R117H 1 R553X + M470V 1 DF508 1 R117H 1 P750L 1 D1152H 1 R31C 1 S1235R 1 PRSS1 4 (25) R122H 3 Unknown* 1 SPINK1 2 (12.5) N34S 2 *One patient was identified as having a PRSS1 mutation, but the specific locus mutation was unknown at the time of publication. Login to comment
181 Among these patients, 9 separate mutations were discovered, the most common of which were DF508, R297Q, and R117H. Login to comment

PMID: 22094894 [PubMed] Sultan M et al: "Genetic prevalence and characteristics in children with recurrent pancreatitis."

No. Sentence Comment

78 Six patients were heterozygous for the CFTR mutation (F508del, R297W, D1152H, R297Q, and I148T). Login to comment
137 Other mutations (R297Q, D1152H, R297Q, and I148T) may be present in CF and CFTR-related disorders such as pancreatitis and obstructive azoospermia (25). Login to comment
145 CFTR mutations and functional consequences CFTR mutations Clinical significance (reference) F508 del Cystic fibrosis (21) 2789 þ 5G>A Cystic fibrosis (21) 5T CFTR-related disorder (pancreatitis, obstructive azoospermia) (21) R533X Cystic fibrosis (22) A349V Unknown clinical significance (26) p.L997F Unknown clinical significance (21), possible CFTR-related disorder (pancreatitis) (7) R297Q Unknown clinical significance (21) D1152H Cystic fibrosis and CFTR-related disorder (21) I 148T Cystic fibrosis (27) CFTR ¼ cystic fibrosis transmembrane conductor regulator. 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

106 However, only the mutations I148T, I175V, G178R, E193K, and R297Q allowed wild-type-like maturation of the protein to the fully glycosylated 170 kDa species (band C). 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
190 I148T, I175V, and R297Q did not adversely affect the processing, gating, or conductance of CFTR. Login to comment
199 The entire CFTR gene was not sequenced in patients with mutations I148T, I175V, or R297Q when these mutations were published. Login to comment
204 In contrast, R297Q, the only CF-associated mutation that could be evaluated in CL2 or deletion of CL2 (18), apparently had little effect on the chloride channel activity of CFTR, as was shown previously for mutations in CL4 (20, 22). Login to comment

PMID: 8818956 [PubMed] Tebbutt SJ et al: "An ovine CFTR variant as a putative cystic fibrosis causing mutation."

No. Sentence Comment

2 The equivalent R297Q mutation in exon 7 of the human CFTR gene has been reported in a CF patient. Login to comment
6 However, only a few mutations A B C B C D CD (Io mo0 E eD 1J -T E F G H J K =_ Wild type A to T il1200) _ G to A lO19) R297Q SSCP 3"_-d<303 bp I_ l8*4bo_ di ges l *~~~~~~~~~84bo Figure 1 Pedigree structure of sheep carrying the Gl019A (R297Q) CFTR exon 7 gene variant in the heterozygote state (also a silent polymorphism, A1200T, unpublished data). Login to comment
15 Ewe "G" is heterozygous for the R297Q variant. Login to comment
24 DNA sequence analysis was used to confirm that the R297Q allele is efficiently transcribed (fig 2). Login to comment
26 This is homologous to a putative cystic fibrosis causing mutation (R297Q) reported in a Northern Ireland family.9 Interestingly, the arginine (R297) residue lies in the first membrane spanning domain of the predicted CFTR protein, specifically part of the cytoplasmic loop between the putative transmembrane helices 4 and 5.1 The threonine-arginine-lysine (TRK) peptide in this region is entirely conserved in the predicted polypeptides from all animal species in which the CFTR gene has been characterised,'0 including human, sheep, cattle, mouse, Xenopus, and dogfish. Login to comment
28 The two human CF patients reported to carry the R297Q mutation were aged 6 and 8 years (in 1991). Login to comment
29 Clinically, both patients were similarly affected with mild to moderate chest symptoms and both were receiving pancreatic - enzyme supplements.9 A recent study of a French CF family" has suggested that R297Q represents a rare polymorphism, rather than a disease causing mutation, or that the length of a T tract in intron 8 may play a role in influencing the severity ofthe R297Q allele. Login to comment
31 At present, it is uncertain if R297Q is a disease causing mutation. Login to comment
32 Nevertheless, if R297Q in the human CFTR protein does indeed contribute to the cystic fibrosis phenotype, it is tempting to consider that an- ^*K'" other animal species, carrying R297Q in the homozygous state, might also show some of -'('- the symptoms of CF. Login to comment
33 The ewe "G", who is heterozygous for R297Q, seems perfectly healthy. Login to comment
34 We are establishing a breeding programme to obtain lambs that are homozygous for the R297Q variant. Login to comment
57 9 Graham C, Goon P, Hill A, Cutting G, Curristan S, Nevin N. Identification of a new mutation (R297Q) in exon 7 of the CFTR gene in a Northern Ireland family. Login to comment
61 11 Dorval I, Jezequel P, Chauvel B, et al. French CF family genotype analysis shows that the R297Q mutation is a rare polymorphism. Login to comment
63 12 Dorval I, Jezequel P, Roussey M, et al. A French CF family genetic analysis shows that the R297Q associated with the T7 allele in the intron 8 polypyrimidine track is not involved in the CF disease. Login to comment
25 DNA sequence analysis was used to confirm that the R297Q allele is efficiently transcribed (fig 2). Login to comment
27 This is homologous to a putative cystic fibrosis causing mutation (R297Q) reported in a Northern Ireland family.9 Interestingly, the arginine (R297) residue lies in the first membrane spanning domain of the predicted CFTR protein, specifically part of the cytoplasmic loop between the putative transmembrane helices 4 and 5.1 The threonine-arginine-lysine (TRK) peptide in this region is entirely conserved in the predicted polypeptides from all animal species in which the CFTR gene has been characterised,'0 including human, sheep, cattle, mouse, Xenopus, and dogfish. Login to comment
30 Clinically, both patients were similarly affected with mild to moderate chest symptoms and both were receiving pancreatic - enzyme supplements.9 A recent study of a French CF family" has suggested that R297Q represents a rare polymorphism, rather than a disease causing mutation, or that the length of a T tract in intron 8 may play a role in influencing the severity ofthe R297Q allele. Login to comment
35 We are establishing a breeding programme to obtain lambs that are homozygous for the R297Q variant. Login to comment
60 Identification of a new mutation (R297Q) in exon 7 of the CFTR gene in a Northern Ireland family. Login to comment
65 11 Dorval I, Jezequel P, Chauvel B, et al. French CF family genotype analysis shows that the R297Q mutation is a rare polymorphism. Login to comment
67 12 Dorval I, Jezequel P, Roussey M, et al. A French CF family genetic analysis shows that the R297Q associated with the T7 allele in the intron 8 polypyrimidine track is not involved in the CF disease. Login to comment

PMID: 8956039 [PubMed] Hughes DJ et al: "Mutation characterization of CFTR gene in 206 Northern Irish CF families: thirty mutations, including two novel, account for approximately 94% of CF chromosomes."

No. Sentence Comment

46 Mutations R297Q, 557delT, and 3849G>A, first identified in Northern Irish CF patients, were identified by PCR assays and direct sequencing (Graham et al., 1991, 1992;Cutting et al., 1992), whereas E60X, 3659delC, and N1303K were found by automated fluorescent sequencing. Login to comment
53 35%) PAGE (278) Kerem et al.. 1989AF508 G551D R117H R560T G542X 621+1G>T A1507 E60X 3659delC R553X 3120G>A 1l54insTC 2789+5G>A N1303K MlI(G>T) QW P67L 557delT 711+3A>G L206W R297Q V520F V562L Y563N Y917C R1162X 3849G>A 3849 +10kbC>T 3850-1GBA W1282X 280 21 17 12 9 9 7 3 2 1 68.0 5.1 4.1 2.9 2.2 2.2 1.7 0.7 0.5 0.24 17-32-13 (38;27%j 17-31-13(24,17%) 16-07-17 16-30-13 plus14 rare haplotypes (29) 16-07-17 23-33-13 (4) 22-31-13 (2) 21-31-13 17-07-17 (5) 16-31-13 16-35-13 17-58-13 17-35-13 16-07-17 17-07-17 23-29-13 (1) 23-31-13 (1) 16-07-17 16-31-13 16-07-17 15-29-13 16-33-13 16-07-17 17-07-17 16-07-17 16-07-17 16-30-13 16-32-17 17-31-13 16-31-14 16-46-13 16-30-14 17-07-17 DGGE(2) ' RD ASO's (11) DGGE(6) RD AR (8) DGGE (1) RD PAGE (5) DGGE (2) SEQ SEQ (2) DGGE (1) RD DGGE DGGE DGGE SEQ DGGE DGGE DGGE SEQ DGGE DGGE SEQ DGGE DGGE DGGE DGGE DGGE SEQ RD DGGE DGGE Cutting et al.. 1990 Dean et al.. 1990 Kerem et al., 1990 Kerem et al.. 1990 Zielenski et al., 1991 Kerem et al.. 1990 Malone et al., CFGAC Kerem et al., 1990 Cutting et al., 1990 Zielenski et al., CFGAC lannuzzi et al., 1991 Highsmith et al., 1990 Osborne et al., 1991 this study Savov et al., 1994 Hamosh et al., CFGAC Graham et al., 1992 Petreska et al., CFGAC Claustres et al., 1993 Graham et al., 1991 Jones et al.. 1992 this study Kerem et al.. 1990 Edkins & Creegan, CFGAC Gasparini et al., 1991 Cutting et al.. 1992 Highsmith et al., 1994 Audriizet et al., 1993 Vidaud et al., 1990 "Numbers in parentheses after the microsatellite haplotypes refer to the number of alleles haplotyped when not all of the available chromosomeswere typed. Login to comment
74 441delA, 557delT 711+1G>T, 711+3A>G H199Y, L206W 977insA R297Q 1078delT,R334W, 1154insTC, R347P W401X l46linsAGAT 1525- 1G>A, A1507, AI5071AF508. Login to comment

PMID: 8889582 [PubMed] Hughes D et al: "Fluorescent multiplex microsatellites used to define haplotypes associated with 75 CFTR mutations from the UK on 437 CF chromosomes."

No. Sentence Comment

74 CF 8CA-17bTA-17bCA Mutation chromosomes % Normal Laboratoryb Reference' HaplotVpe 1)15-29-13 557delT Nl Graham et al.. 1992 21 16-07-17 MU (G>T) 3) 16-24-13 4) 16-25-13 5) 16-29-13 6) 16-30-13 7) 16-30-14 8) 16-31-13 9) 16-31-14 10) 16-32-13 12) 16-33-13 13) 16-34-13 14) 16-35-13 11)16-32-17 15)1645-13 16) 1646-13 17) 1646-14 19) 17-07-17 18)16-53-13 20)17-29-14 21) 17-31-13 22) 17-32-13 23) 17-35-13 24) 17-51-11 25) 17-55-13 27) 17-58-13 28) 21-31-13 29) 22-31-13 31)23-22-17 26) 17-56-13 30) 22-33-13 32) 23-29-13 33)23-31-13 34)23-32-13 35)23-33-13 36)23-34-13 37) 23-36-13 38)24-22-17 39) 24-31-13 182delT P67L R75X L206W 1154insTC 146linsAGAT Q493x V520F 1717-1G>A G551D R560T V562L R709X S1196X L1254X R1283M G85E 2184insA 711+lG>T 3495delA 4279insA SlOR L88S R117C R117H G178R 1717-1G>A Y563N W1098R G1123R 3850- 1G>A E6OX %%deIT 1138insG R34P 2183AA>G 2184delA R1158X 1078delT R1162X 3849G>A Q141W R347P Y917C G2iX 711+3A>G 441delA 3130de115 3659delC 1898+1G>A R709X 2711delT R1158X E92K 3849+lOkbC>T 2118delAACT 4048insCC 296+1 2 T S Q22OX R297Q A1507 2789+5G>A 3120+1G>A W128W 1811+lG>C AF508 E831X R116W AF508 W846X1 3120G>A R785X R553X R553X R553X 621+1G>T G542X G542X Y1182X N1303K AF508 G54W 3041delG 1525-1G>A N1303K G542X G542X G542X 394delTT R709X N1303K 1 1 1 2 1 1 4 2 3 4 2 26 8 1 1 1 1 1 8 1 1 1 1 1 1 1 19 1 2 1 1 1 1 7 1 1 2 1 1 2 1 1 1 1 1 1 1 1 2 1 1 7 4 1 2 1 1 2 1 1 4 Asian 1 2 1Asian 5 4 i Afro-Caribbean 5 1 42 (19%) 1 1 57 (26%) 1 2 1 1 1 2 12 2 11.4 0.4 4.9 16.3 1.1 3.8 1.9 10.6 2.3 1.5 2.3 1.5 2.7 4.5 0.4 0.8 0.8 0.4 0.8 0.4 1 2 1 7 1 1 1Asian 1 1.5 0.8 0.8 NI G NI, M M NI NI. Login to comment

PMID: 7551394 [PubMed] Friedman KJ et al: "Screening Young syndrome patients for CFTR mutations."

No. Sentence Comment

78 Of the 13 Young syndrome patients, we identified one (Patient 5) who was het- CBAVD Dl152H D1270N G576A* R75Q* P67L Rl17H 3849 + 10 KB C > T G551S Rl17H Pancreatic Sufficient, Moderate Pulmonary Symptoms, Normal Sweat Chloride Concentrations Pancreatic Sufficient, Moderate Pulmonary Symptoms R347P 2789 + 5 G > A R334W G85E R347H R347L Rl17H G91R A455E S945L Y563N Q1291H R297Q R352Q L1065P 3850-3 T > G F1286S 3849 + 10 KB C > T TABLE 1 CFTR MUTATION SCREENING PANEL Severe M508 G551D R553X N1303K W1282X G542X 1717-1 G > A ~1507 R560T 3659deiC 621 + 1 G > T S549N TABLE 2 CLINICAL FEATURES OF YOUNG SYNDROME PATIENTS Patient Age Sweat CI- FEV, Paranasal Sputum No. Login to comment

PMID: 7535745 [PubMed] Hughes D et al: "Fluorescent multiplex microsatellites used to identify haplotype associations with 15 CFTR mutations in 124 Northern Irish CF families."

No. Sentence Comment

24 All mutations have a distinct associated haplotype, except G551D/R560T, which are both on 16-7-17, and I507/R297Q on 17-7-17. Login to comment
25 Nine haplotypes having specific CF mutations are not present in normal chromosomes Mutation Alleles tested (%) AF508 41 (34.2) 32 (26.7) 22 (18.3) G551D 16 R560T 08 621 + 1G > T 08 Rll7H 05 G542X 03 02 E60X 02 M507 02 R297Q 01 R553X 01 3849 G > A 01 N1303K 01 3659delC 01 557delT 01 Q2X 01 Frequency Haplotype of mutation in % 8AC 17AT 17AC 463 % in normal chromosomes 58.0 23 31 13 - 17 32 13 01 17 31 13 - 4.0 16 07 17 03 2.5 16 07 17 03 1.7 21 31 13 - 2.1 16 30 13 16 1.7 23 33 13 01 22 31 13 - 0.6 16 31 13 03 0.8 17 07 17 08 0.2 17 07 17 08 0.2 17 58 13 - 0.2 16 31 14 - 0.4 23 31 13 - 0.2 16 35 13 03 0.2 15 29 13 - 0.2 23 34 13 01 Table 2 Frequent haplotypes generated from normal and uncharacterised CF chromosomes in N. Ireland. Login to comment

PMID: 8825494 [PubMed] Zielenski J et al: "Cystic fibrosis: genotypic and phenotypic variations."

No. Sentence Comment

593 Not surprisingly, Rl17H is associated with CF only when the allele also contains Table 2 Examples of complex alleles in the CfTR gene Principal Second site mutationa Location alteration Location Reference R75X exon 3 125G --.. C promoter 57 405 + IG --.. A intron 3 3030G --.. A exon 15 57 R1l7H exon 4 129G --.. C promoter 203 RI17H exon 4 IVS8 : 5T or 7T intron 8 101 R297Q exon 7 IVS8 : 5T or 7T intron 8 60 aF508 exon 10 R553Q exon II 59 aF508 exon 10 1I027T exon I7a 57 8F508 exon 10 deletion of D7S8 500 kb 3' of 186 CfTR S549N exon II R75Q exon 3 205a L619S exon 13 1716G � A exon 10 57 G628R (G � C) exon 13 SI235R exon 19 47 2184insA exon 13 IVS:5T exon 9 J Zielenski, J Bal, 0 Markiewicz, L-C Tsui, unpublished data A800G exon 13 IVS8 : 5T or 7T intran 8 31 S912L exon 15 GI244V exon 20 149 GlO69R exon 17b L88X exon 3 149 3732deiA exon 19 Kl200E exon 19 70 3849 + IOkbC � intron 19 R668C exon 13 57 T SI251N exon 20 F508C exon 10 94 The status of principal mutation may not be clear in every case; e.g. G628R(G --> C) vs S1235R. Login to comment
595 RI17H in combination with 5T can apparently produce only -40% of the CFfR transcript in full-length mRNA, whereas RI17H with 7T gives -90% (83), A similar modulating effect has been observed for R297Q, which can be associated with either 5T or 7T (60). Login to comment
911 A french CF family genetic analysis shows that the R297Q associated with the T7 allele in the intron 8 polypyrimidine track is not involved in the CF disease. Login to comment

PMID: 7525963 [PubMed] Chevalier-Porst F et al: "Mutation analysis in 600 French cystic fibrosis patients."

No. Sentence Comment

21 Among the 104 other CFTR mutations tested on the 373 non-AF508 CF chromosomes, none of the following 58 mutations were found: G91R, 435 insA, 444delA, D11OH, 556delA, 557delT, R297Q, 1154insTC, R347L, R352Q, Q359K/T360K, 1221delCT, G480C, Q493R, V520F, C524X, 1706dell7, S549R (A-C), S549N, S549I, G551S, 1784delG, Q552X, L558S, A559T, R560T, R560K, Y563N, P574H, 2307insA, 2522insC, 2556insAT, E827X, Q890X, Y913C, 2991de132 (Dork et al, personal communication), L967S, 3320ins5, 3359delCT, H1085R, R1158X, 3662delA, 3667del4, 3667ins4, 3732delA, 3737delA, W1204X, 3750delAG, I 1234V, Q1238X, 3850- 3T-+G, 3860ins31, S1255X, 3898insC, D1270N, R1283M, F1286S, 4005 + I G-A. Forty-six other mutations were found on at Distribution of CFTR mutations found in our sample ofpopulation (1200 CF chromosomes) Mutations tested No of CF chromosomes Haplotypes Method with the mutation XV2C-KM19 (% of total CF alleles) Exon 3: G85E 4 (033) 3C HinfI/ASO394delTT 2 2B PAGEExon 4: R117H 1 B ASOY122X 2 2C MseI/sequenceI148T 1 B ASO621+IG-J* 1 B MseIIASOExon 5: 711+1G--T 8(07) 8A ASOExon 7: AF311 1 C PAGE/sequencelO78delT 5 (0-42) 5C PAGE/ASOR334W 5 (0-42) 2A,2C,ID MspIlASOR347P 5 (042) 5A CfoI/NcoIR347H 1 Cfol/sequenceExon 9: A455E 1 B ASOExon 10: S492F I C DdeI/sequenceQ493X 1 D ASOl609deICA 1 C PAGE/Ddel/sequenceA1507 3 (025) 3D PAGE/ASOAF508 827 (69) 794B,30D,2C,IA PAGEl677delTA 1 A PAGE/sequenceExon I11: 1717-IG--.A 16(1-3) 14B Modified primers + AvaIIG542X 40 (3-3) 29B,5D,2A Modified primers + BstNiS549R(T--*G) 2 2B ASOG551D 3 (025) 3B HincII/Sau3AR553X 10(0-8) 6A,1B,2C,ID Hincll/sequenceExon 12: 1898+IG--A 1 C ASO1898+ IG-C 2 IC ASOExon 13: l9l8deIGC 1 A PAGE/sequence1949de184 I C PAGE/sequenceG628R(G-+A) 2 2A Sequence2118de14 I c PAGE/sequence2143de1T 1 B PAGE/modified primers2184de1A+2183A--*G 11 (0-9) lIB PAGE/ASO2184de1A 1 ASOK710X 3 (025) IC XmnI2372de18 1 B PAGE/sequenceExon 15: S945L 1 C TaqlExon 17b:L1065P I MnlIL1077P 1 A ASOY1092X 3 (025) 2C,IA Rsal/ASOExon 19: RI1162X 6 (0-5) 5C,IA DdeI/ASO3659delC 3 (025) 3C ASOExon 20: G1244E 2 2A MboIIS1251N 2 2C RsaI3905insT 4 (0-33) 4C PAGE/ASOW1282X 18 (105) 15B,1D MnlI/ASOR1283K 1 C Mnll/sequenceExon 21: N1303K 22 (1-8) 18B,lA,ID Modified primers+BstNI 47 mutations 1031 (85 9) least one CF chromosome (table): 21 of them are very rare as they were found on only one CF chromosome in our population. Login to comment

PMID: 25033378 [PubMed] LaRusch J et al: "Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis."

No. Sentence Comment

116 CFTR variant %Cases %Uctrls OR p-value %Cases w/N34S OR w/N34S p-value w/N34S F508C 0.5 0.3 1.58 0.21 0.0 0.00 0.67 R1162L 0.5 0.5 1.13 0.29 1.8 4.03 0.17 I1027T 0.5 0.3 1.99 0.17 0.0 0.00 0.70 R31C 0.3 0.7 0.42 0.088 0.0 0.00 0.52 I148T 0.3 0.4 0.75 0.27 0.0 0.00 0.63 R297Q 0.3 0.2 1.89 0.21 0.0 0.00 0.76 R74W 0.2 0.2 0.85 0.29 0.0 0.00 0.71 F1052V 0.1 0.2 0.63 0.27 0.0 0.00 0.76 I807M 0.1 0.1 1.26 0.30 0.0 0.00 0.83 R258G 0.1 0.1 1.26 0.30 0.0 0.00 0.83 G1069R 0.1 0.0 0.13 0.0 V201M 0.0 0.1 0.17 0.0 0.00 0.83 Of the 81 CFTR mutations tested in the cohort, 43 were observed at least once in cases or controls. Login to comment
269 67 SNPs (125GtoC, 1716G.A, 1717-1G.A, 1898+1G.A, 2183AA.G, 2184delA, 2789+5G.A, 3120+1G.A, 3659delC, 3849+10kbC.T, 621+ 1G.T, 711+5G.A, A455E, D110H, D1152H, D1270N, D443Y, D579G, F1052V, F1074L, F508C, F508del, G1069R, G1244E, G1349D, G178R, G542X, G551D, G551S, I1131L/V, I148T, I336K/T, I507del, I807M, IVS8T5, K1180T, L1065P, L967S, L997F, M1V, M470V, M952I, M952T, N1303K, P67L, Q1463Q, R1070Q, R1162X, R117C, R117H, R170H, R258G, R297Q, R31C, R352Q, R553X, R668C, R74W, R75Q, S1235R, S1255P, S485R, S977F, T338I, T854T, V201M, W1282X) were multiplexed into 6 wells; 14 SNPs (S492F, S945L, R74Q, R560T, R1162L, G85E, I1027T, R334W, R347P, G576A, 711+1G.T, 1001+11C.T, P1290P, 3199del6) were ascertained separately via TaqMan Gene Expression Assays, with repeat confirmation of all positive results. Login to comment

PMID: 9691989 [PubMed] Tebbutt SJ et al: "Genetic variation within the ovine cystic fibrosis transmembrane conductance regulator gene."

No. Sentence Comment

7 In addition to the mutation R297Q reported previously, we have found several interesting variants, including intronic DNA variants and exonic polymorphisms. Login to comment
93 d; R297Q mutation reported previously 14 . Login to comment
129 w x CF-causing mutation R297Q found in humans 19 w x and has previously been reported by our group 14 . Login to comment
130 R297Q has since been found in two other ewes and all these animals have been involved in an embryo transfer programme in order to increase the number of animals carrying R297Q. Login to comment
131 Several carrier ewes as well as a carrier ram have subsequently been generated, and will be mated in order to produce a lamb homozygous for R297Q. Login to comment
141 Apart from the R297Q mutation, none of the ovine CFTR variants have equivalents in the human CFTR d; . Login to comment