ABCMdb

ABCC7 p.Arg334Gln

None has been submitted yet.

Publications

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

No. Sentence Comment

394 They are positively charged amino acids [171], conserved across species and associated with CF: R334Q/W and R347C/H/L/P. Login to comment

PMID: 11379874 [PubMed] Le Marechal C et al: "Complete and rapid scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by denaturing high-performance liquid chromatography (D-HPLC): major implications for genetic counselling."

No. Sentence Comment

114 At 56°C, the profiles of ∆F508 and M470V are identical 295 Table 2 Novel nucleotide changes identified in the CFTR gene and detected by D-HPLC Exon/ intron Mutant name Nucleic acid change Amino acid change Effect on amino acid sequence Patient 1 185+1 G to T G to T at 185+1 Splicing CF patient 2 186 - 13 C to G C to G at 186-13 Silent CF patient 2 211 Del G Deletion of G at 211 Frameshift CF patient 2 237 Ins A Insertion A at 237 Frameshift CF patient 2 296+2 T to C 296+2 T to C Splicing CF patient 3 W 57 X2 G to A at 303 Trp to Stop at 57 (TGG to TGA) Nonsense CF patient 3 306 InsA Insertion of A at 306 Frameshift CF patient 3 306 Ins C Insertion of C at 306 Frameshift CF patient 3 W 79 X G to A at 368 Trp to Stop at 79 (TGG to TAG) Nonsense CF patient 4 A 96 E C to A at 419 Ala to Glu at 96 (GCA to GAA) Missense CF patient 4 L 127 X T to G at 512 Nonsense CF patient 4 541 Del CTCC Deletion of CTCC at 541 Leu to Stop at 127 (TTA to TGA) Frameshift CF patient 5 L 165 S T to C at 626 Leu to Ser at 165 (TTA to TCA) Missense CF patient 5 R 170 C C to T at 640 Arg to Cys at 170 (CGT to TGT) Missense Control 6a L 206 F G to T at 750 Leu to Phe at 206 (TTG to TTT) Missense CF patient 6a A 209 S G to T at 757 Ala to Ser at 209 (GCA toTCA) Missense CF patient 6a A 209 A A to G at 759 Ala to Ala at 209 (GCA to GCG) Silent CF patient 6a C 225 X T to A at 807 Cys to Stop at 225 (TGT to TGA) Nonsense CF patient 6a G 241 R G to A at 852 Gly to Arg at 241 (GGG to AGG) Missense CF patient 6b 905 Del G Deletion of Gat 905 Frameshift CF patient 7 A 309 A C to G at 1059 Ala to Ala at 309 (GCC to GCG) Silent Control 7 V 322 M G to A at 1096 Val to Met at 322 (GTG to ATG) Silent CF patient 7 R 334 Q G to A at 1133 Arg to Gln at 334 (CGG toCAG) Missense Control 7 Q 353 H A to C at 1191 Gln to His at 353 (CAA to CAC) Missense CF patient 7 1248+1 G to C G to C at 1248+1 Splicing CF patient 8 L 383 L G to A at 1281 Leu to Leu at 383 (TTG to TTA) Silent Control 8 W 401 X G to A at 1334 Trp to Stop at 401 (TGG to TAG) Nonsense CF patient 8 E 403 D G to C at 1341 Glu to Asp at 403 (GAG to CAG) Missense CF patient 9 1367 Del C Frameshift CF patient 10 1525 - 2 A to G Deletion of C at 1367 Splicing CF patient 10 G 480 G T to C at 1572 Gly to Gly at 480 (GGT to GGC) Silent CF patient 10 1576 Ins T Insertion of T at 1576 Frameshift CF patient 10 H 484 R A to G at 1583 His to Arg at 484 (CAC to CGC) Missense Neonatal hypertrypsinaemia 10 I506 V A to G at 1648 Ileto Val at 506 (ATC to GTC) Silent Control 11 1717 - 19 T to C T to C at 1717-19 Splicing ? Login to comment

PMID: 11585852 [PubMed] Smith SS et al: "CFTR: covalent and noncovalent modification suggests a role for fixed charges in anion conduction."

No. Sentence Comment

187 MTSES, MTSET, or MTSEA (100 ␮M or 1 mM) were added to the perfusate of oocytes expressing R334A or R334Q CFTR and produced no discernible effect on conductance (unpublished data). Login to comment
313 The conductance of oocytes expressing R334Q CFTR was independent of pH and was not greatly altered by NEM. Login to comment
317 Exposure of oocytes expressing R334Q CFTR to MTSHE produced only small changes in conductance. Login to comment

PMID: 12679372 [PubMed] Gong X et al: "Molecular determinants and role of an anion binding site in the external mouth of the CFTR chloride channel pore."

No. Sentence Comment

53 Block of wild-type, R334C-, R334E-, R334H-, R334K-, R334L- and R334Q-CFTR by 100 mM and 1 mM intracellular Au(CN)2 _ are compared in Fig. 4B. Login to comment

PMID: 15070876 [PubMed] Dayangac D et al: "Mutations of the CFTR gene in Turkish patients with congenital bilateral absence of the vas deferens."

No. Sentence Comment

42 2 (2.0)a This study R74W Exon 3 C®T at 352 Amino acid substitution 1 (1.0) Claustres et al. 1993b 359insT Exon 3 Insertion of T within 360±365 Truncation 1 (1.0) Claustres et al. 1995* A349V Exon 7 C®T at 1178 Amino acid substitution 1 (1.0) Audrezet et al. 1993 R334Q Exon 7 G®A at 1133 Amino acid substitution 1 (1.0) Ferec et al. 1994* T388M Exon 8 C®T at 1295 Amino acid substitution 1 (1.0) Zielenski et al. 1996 IVS8-6T Intron 8 Deletion of T between 1342±12 and 1342±6 Aberrant splicing? Login to comment
47 *The following mutations were previously reported as personal communications to the CF Genetic Analysis Consortium (http://www.genet.sickkids.on.ca): 359insT by Claustres M, Desgeorges M, Romey M-C; R334Q by FeÂrec C, Quere I, Verlingue C, Raguenes O, AudreÂzet M-P, Mercier B; T388M by Zielenski J, Markiewicz D, Tsui L-C, Rawashdeh M, Khateeb M; E831X by FeÂrec C, Quere I, Audrezet MP, Verlingue C, Guillermit H, Mercier B; M952I by Girodon E, Costes B, Cazeneuve C, Ghanem N, Goossens M; R1070W by Macek M Jr, Sedriks S, Kiesewetter S, Cutting GR; D1152H by Highsmith WE Jr, Burch L, Friedman KJ, Wood BM, Spock A, Silverman LM, Knowles MR. Login to comment
72 CFTR genotypes in 51 patients with congenital bilateral absence of the vas deferens Mutation genotypes IVS8-(TG)mTn M470V n (%) Two mutations detected: D1152H/D1152H (TG)11 7T/ (TG)11 7T V/V 5 (9.8) IVS8-5T/IVS8-5T (TG)13 5T/ (TG)13 5T M/M 2 (3.9) (TG)12 5T/ (TG)13 5T M/V 1 (1.9) (TG)12 5T/ (TG)12 5T V/V 1 (1.9) IVS8-5T/D1152H (TG)12 5T/ (TG)11 7T V/V 2 (3.9) IVS8-5T/DF508 (TG)12 5T/ (TG)10 9T M/V 2 (3.9) IVS8-5T/2789+5G®A (TG)12 5T/ (TG)10 7T M/V 2 (3.9) IVS8-5T/365insT (TG)13 5T/ (TG)11 7T M/V 1 (1.9) IVS8-5T/D110H (TG)12 5T/ (TG)11 7T M/V 1 (1.9) IVS8-5T/E585X (TG)12 5T/ (TG)10 7T M/V 1 (1.9) IVS8-5T/2752-15C®G (TG)12 5T/ (TG)11 7T V/V 1 (1.9) IVS8-5T/M952I (TG)12 5T/ (TG)10 7T M/V 1 (1.9) IVS8-5T/3120+1G®A (TG)12 5T/ (TG)11 7T V/V 1 (1.9) D1152H/A349V (TG)10 7T/ (TG)11 7T M/V 1 (1.9) D1152H/2789+5G®A (TG)10 7T/ (TG)11 7T M/V 1 (1.9) D1152H/G1130A (TG)10 7T/ (TG)11 7T M/V 1 (1.9) CFTRdele2(ins186)/ IVS8-6T (TG)13 6T/ (TG)11 7T M/V 1 (1.9) CFTRdele2(ins186)/D110H (TG)11 7T/ (TG)11 7T V/V 1 (1.9) E831X/D110H (TG)11 7T/ (TG)11 7T V/V 1 (1.9) E831X/1677delTA (TG)11 7T/ (TG)11 7T V/V 1 (1.9) R334Q/R347H (TG)11 7T/ (TG)11 7T V/V 1 (1.9) 1767del6/1767del6 (TG)11 7T/ (TG)11 7T V/V 1 (1.9) 3041-15T®G/3041-15T®G (TG)12 7T/ (TG)12 7T M/M 1 (1.9) 3041-13del7/3041-13del7 (TG)10 7T/ (TG)10 7T M/M 1 (1.9) R1070W/3272-26A®G (TG)10 7T/ (TG)11 7T M/V 1 (1.9) I853F/L997F (TG)11 7T/ (TG)10 9T V/V 1 (1.9) One mutation detected: L997F/? Login to comment

PMID: 15832355 [PubMed] Castellani C et al: "Cystic fibrosis carriers have higher neonatal immunoreactive trypsinogen values than non-carriers."

No. Sentence Comment

23 A similar comparison was made between two subgroups including, respectively, 247 carriers of class I, II, and III mutations (in fact the same as in the pancreatic insufficiency mutation group) and 43 carriers of class IV and V mutations [Welsh and Smith, 1993]; mutation R334Q was not included because of difficulties in allocating it to a specific class. Login to comment
40 Distribution and Classification of the Tested Mutations in the Normal IRT Heterozygote Population Under Study Mutations Type of mutation Class of mutation Number of cases F508del Severe II 161 N1303K Severe II 19 G542X Severe I 19 711 þ 5G > A - V 15 R117H Mild IV 13 R1162X Severe I 13 R553X Severe I 11 G85E - IV 8 2183AA > G Severe I 8 1717-1G > A Severe I 8 R334Q Mild - 4 Q552X Severe I 4 W1282X Severe I 3 2789 þ 5G > A Mild V 2 1898 þ 3A > G Mild V 2 T338I Mild IV 1 R709X Severe I 1 R347H Mild IV 1 3849 þ 10KbC > T Mild V 1 Total 294 Other tested mutations: 1078delTn1609delCAn1717-8g/an394delTTn457TAT> Gn541delCn621 þ 1g/tn711 þ 1g/tnA559TnDI507nG551DnR1158XnR334Wn R347PnR352QnS549InS549NnS549Ra/cn2790-2G > An1811 þ 1.2KbA > G; 711þ5G > A and G85E not categorized in type of mutation; R334Q not categorized in class of mutation. Login to comment

PMID: 15880796 [PubMed] Kerem E et al: "Pharmacological induction of CFTR function in patients with cystic fibrosis: mutation-specific therapy."

No. Sentence Comment

58 C-D565G II DF508 D1507 S549R S549I S549N S549R S945D S945L H1054D G1061R L1065P R1066C R1066M L1077P H1085R N1303K G85E III G551D S492F V520F R553G R560T R560S Y569D IV R117H, R117C, R117P, R117L D1152H, L88S, G91R, E92K, Q98R, P205S, L206W, L227R, F311L, G314E, R334W, R334Q, I336K, T338I, L346P, R347C, R347H, R347L, R347P, L927P, R1070W, R1070Q V 3849 þ 10 kb C ! 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

47 CFTR gene alterations were first scored by PCR and reverse dot blot (Chehab and Wall, 1992), targeted to the detection of the following mutations: ∆F508, G85E, 541∆C, D110H, R117H, 621+1G→T, 711+5G→A, R334W, R334Q, T338I, 1078∆T, R347H, R352Q, ∆I507, 1609∆CA, E527G, 1717-1G→A, 1717-8G→A, G542X, R347P, S549N, S549R A→C, Q552X, R553X, A559T, D579G, Y577F, E585X, 1898+3A→G, 2183AA→G, R709X, 2789+5G→A, 3132∆TG, 3272-26A→G, L1077P, L1065P, R1070Q, R1066H, M1101K, D1152H, R1158X, R1162X, 3849+10KbC→T, G1244E, W1282R, W1282X, N1303K and 4016∇T. Login to comment
79 Concerning instead the mutations found in the male group, besides ∆F508 the following have been found: 2789+5 g/a, 711+5 g/a, D1152H, G85E, N1303K, Q552X, R1158X, R117H, R334Q, R334W and R553X. Login to comment
101 Mutations Women (987) Men (867) N IVS8-T genotype N IVS8-T genotype ∆F508 16 15(7/9); 1(9/9) 26 15(7/9)*; 11(5/9) N1303K 4 4(7/9) 1 7/7 3849+10KbC→T 1 5/7 1 5/7 G542X 2 7/9 1 7/9† 2183AA→G 2 7/7 4 7/7 R553X 2 7/7 0 - R1162X 2 7/7 6 5(7/7)‡; 1(7/9) D1152H 0 - 3 2(7/7); 7/9† 711+5G→A 0 - 3 7/7 1717-8G→A 0 - 1 5/7 1717-1G→A 1 7/7 0 - Y577F 0 - 1 7/7 R117H 1 7/7 1 7/9* 621+3A→G 1 7/9 0 - W1282X 1 7/7 0 - deltaI1507 1 7/7 0 - T3381 1 7/7 1 7/9 R1066H 0 - 1 7/7§ R334Q 0 - 1 7/9 2789+5G→A 1 7/7 2 7/7‡§ Total 36¶ 53¶ records, all these mutations are normally found in trans with respect of 5T. Login to comment

PMID: 17673962 [PubMed] Zhou JJ et al: "Direct and indirect effects of mutations at the outer mouth of the cystic fibrosis transmembrane conductance regulator chloride channel pore."

No. Sentence Comment

72 Neutralization of a third pore-forming positive charge, in the R334Q mutant, was also associated with significant weakening of the blocking effects of internal Pt(NO2)4 2À (Figs. 1, 2). Login to comment
74 However, unlike K95Q and R303Q, the R334Q mutant weakened Pt(NO2)4 2À block at low, but not high, extracellular ClÀ concentration (Fig. 2). Login to comment
75 This difference likely results from the fact that the R334Q mutation also apparently removes the sensitivity of block to extracellular ClÀ concentration (Figs. 1c, 2). Login to comment
81 Mean of data from three to eight patches. Fitted lines are to equation 1, with the following parameters: wild type 4 mM external ClÀ , Kd(0) = 85.8 lM, zd = À0.201; wild type 154 mM external ClÀ , Kd(0) = 387 lM, zd = À0.344; K95Q 4 mM external ClÀ , Kd(0) = 403 lM, zd = À0.130; K95Q 154 mM external ClÀ , Kd(0) = 978 lM, zd = À0.227; R303Q 4 mM external ClÀ , Kd(0) = 300 lM, zd = À0.096; R303Q 154 mM external ClÀ , Kd(0) = 904 lM, zd = À0.197; R334Q 4 mM external ClÀ , Kd(0) = 286 lM, zd = À0.330; R334Q 154 mM external ClÀ , Kd(0) = 256 lM, zd = À0.307. Login to comment
85 Figure 3 shows the blocking effects of internally applied Pt(NO2)4 2À in six different channel mutants (R334C, R334E, R334H, R334K, R334L, R334Q) under conditions of both low (Fig. 3a) and high (Fig. 3b) extracellular ClÀ concentration. Login to comment
91 With elevated extracellular ClÀ , the Kd(0) was significantly increased only in R334C and R334E; not significantly altered in R334K, R334L and R334Q; and significantly decreased in R334H (Fig. 5b). Login to comment
93 These R334 mutations also exhibited a weakened sensitivity of blocker voltage dependence (quantified as -zd, Fig. 5) to external ClÀ concentration (Fig. 5c), although because of the small magnitude of this effect only R334C, R334H and R334Q reached a level of statistical significance (Fig. 5c). Login to comment
106 Comparison of the mean Kd estimated for suramin (at 0 mV) shows that R334C, R334E, R334K, R334L and R334Q were all associated with weakened suramin block, with only R334H failing to significantly affect suramin block (Fig. 7). Login to comment
110 As shown in Figure 8, although block by internal Pt(NO2)4 2À is significantly weakened in R334Q, this blocking effect is still sensitive to the presence of Pt(NO2)4 2À ions in the extracellular solution. Login to comment
111 In wild type, addition of 8 mM Pt(NO2)4 2À to the extracellular solution increased mean Kd(0) for intracellular Pt(NO2)4 2À approximately 2.7-fold without significantly altering -zd, while in R334Q this concentration of extracellular Pt(NO2)4 2À increased mean Kd(0) 2.5-fold, again with no significant change in -zd (Fig. 8c). Login to comment
112 Thus, the R334Q mutation practically abolishes the dependence of intracellular Pt(NO2)4 2À block on external ClÀ (Figs. 1c, 2, 5c) without significantly altering its dependence on external Pt(NO2)4 2À (Fig. 8). Login to comment
129 Mean of data from three to eight patches. Fitted lines are to equation 1 as described in Figure 1 for wild type and R334Q and with the following parameters for other channel variants: R334C 4 mM external ClÀ , Kd(0) = 1362 lM, zd = À0.295; R334C 154 mM external ClÀ , Kd(0) = 836 lM, zd = À0.219; R334E 4 mM external ClÀ , Kd(0) = 759 lM, zd = À0.376; R334E 154 mM external ClÀ , Kd(0) = 564 lM, zd = À0.173; R334H 4 mM external ClÀ , Kd(0) = 140 lM, zd = À0.166; R334H 154 mM external ClÀ , Kd(0) = 119 lM, zd = À0.149; R334K 4 mM external ClÀ , Kd(0) = 143 lM, zd = À0.314; R334K 154 mM external ClÀ , Kd(0) = 317 lM, zd = À0.374; R334L 4 mM external ClÀ , Kd(0) = 176 lM, zd = À0.258; R334L 154 mM external ClÀ , Kd(0) = 284 lM, zd = À0.366 extracellular Pt(NO2)4 2À by normalizing current amplitude at the hyperpolarized extreme of the voltage range studied, -80 mV (Fig. 10b). Login to comment
159 These plots represent mean data from four to seven patches. Fitted lines are to equation 1 with the following parameters: wild type, Kd(0) = 2.51 lM, zd = À0.042; R334C, Kd(0) = 18.5 lM, zd = À0.056; R334E, Kd(0) = 25.0 lM, zd = À0.107; R334H, Kd(0) = 3.10 lM, zd = À0.085; R334K, Kd(0) = 6.31 lM, zd = À0.232; R334L, Kd(0) = 4.08 lM, zd = À0.061; R334Q, Kd(0) = 6.64 lM, zd = À0.239 with our previous suggestion that intracellular Au(CN)2 À blocks the channel by interacting directly with R334, several reasons prompt us to suggest that Pt(NO2)4 2À does not interact directly with the arginine side chain at this position. Login to comment
171 a Example leak-subtracted macroscopic current-voltage relationships recorded with 8 mM K2Pt(NO2)4 2À present in the extracellular solution for wild type (left) and R334Q (right), recorded before (control) and after (+ Pt[NO2]4) addition of 300 lM K2Pt(NO2)4 to the intracellular solution. Login to comment
173 Mean of data from three to eight patches. Fitted lines are to equation 1 with the following parameters: wild type (), Kd(0) = 85.8 lM, -zd = 0.201; wild type (d), Kd(0) = 205 lM, - zd = 0.248; R334Q (), Kd(0) = 286 lM, -zd = 0.330; R334Q (d), Kd(0) = 704 lM, -zd = 0.401. c Mean Kd(0) and -zd calculated under these conditions, without extracellular Pt(NO2)4 2À (white bars) and with 8 mM Pt(NO2)4 2À (black bars). Login to comment
214 Furthermore, we suggest that external Pt(NO2)4 2À and external ClÀ destabilize the binding of internal blockers by different mechanisms since the effects of ClÀ , but not Pt(NO2)4 2À , are lost in R334Q. Login to comment
228 ), R334E (5), R334H (j), R334K (), R334L (h), R334Q (u); c wild type (d), K95Q (m), R303Q (Å). Login to comment

PMID: 19897426 [PubMed] Picci L et al: "A 10-year large-scale cystic fibrosis carrier screening in the Italian population."

No. Sentence Comment

48 Forty-seven different CFTR mutations/gene alterations were chosen and analysed: ΔF508, G85E, 541delC, D110H, R117H, 621+1G→T, 711+5G→A, R334W, R334Q, T338I, R347H, R347P, R352Q, S466X, ΔI507, E527G, 1717-1G→A, 1717-8G→A, G542X, S549N, S549R A→C, G551D, Q552X, R553X, D579G, 1874insT, E585X, 1898+3A→G, 2183AA→G, 2184delA, R709X, 2789+5G→A, 3132delTG, 3199del6, 3272-26A→G, L1077P, L1065P, R1066H, M1101K, D1152H, R1158X, R1162X, 3849+10KbC→T, G1244E, W1282X, N1303K and 4016insT. Login to comment
97 CF mutation General adult population MAR population n=1879 n=236 ΔF508 42.6 45.7 2183AA→G 5.9 5.9 R1162X 5.7 8.2 N1303K 5.4 5.9 G542X 4.2 3.7 D1152H 3.9 5.0 R553X 3.7 3.1 R117H 3.3 1.8 711+5G→A 2.8 4.1 Q552X 2.8 0.4 2789+5G→A 2.2 3.1 1717-1G→A 2.6 2.8 E527G 2.4 - G85E 2.4 0.9 R334Q 0.9 0.4 W1282X 0.7 0.9 R334W 0.6 - 1898+3A→G 0.5 0.4 R1158X 0.4 - R1066H 0.4 0.4 T338I 0.4 1.8 3849+10Kb C→T 0.4 1.3 3272-26 A→G - 0.9 3132delTG - 0.9 3659 del C - 0.4 4016 ins T - 0.4 1717-8G→A - 0.4 R347H - 0.4 ΔI507 - 0.4 R1070Q - 0.4 Other (16) 5.4 - Table 2a List of CFTR compound heterozygotes in the adult general population. Mutation Health status Disorder Gender Age (years) Notes and refs ΔF508/A238V Infertile CBAVD M 36 (A) ΔF508/R352W Infertile CBAVD M 45 (A) R553X/R334Q M 38 ΔF508/R347H M 53 [17] S42F/D372E (1251T→G) M 39 (A) (B) ΔF508/D110H Infertile M 38 ΔF508/L1414S (4373T→C) Infertile CBAVD M 44 (A) (B) ΔF508/V201M, D1270N & R74W Infertile CBAVD M 44 (A) [18,19] 2183AA→G/L206W Infertile CBAVD M 40 (A) 711+5G→A/ L206W Infertile CBAVD M 40 (A) Table 2b List of CFTR compound heterozygotes in the population enrolled for medically assisted reproduction. Login to comment

PMID: 20100616 [PubMed] Havasi V et al: "Association of cystic fibrosis genetic modifiers with congenital bilateral absence of the vas deferens."

No. Sentence Comment

68 Portuguese CFTR alleles Spanish CFTR alleles Turkish CFTR alleles 5T 22 F508del 11 5T 20 F508del 14 5T 9 D1152H 14 R334W 5 D443Ya 3 D110H 3 R117H 3 G576Aa 3 F508del 2 S1235R 3 R668Ca 3 3041-11del7 2 N1303K 2 G542X 2 1767del6 2 P205S 2 R117H 2 2789þ5G>A 2 D614G 2 V232D 2 CFTRdele2(ins186) 2 G542X 1 L997F 1 3120þ1G>A 1 L206W 1 H609R 1 G1130A 1 V562I 1 N1303H 1 M952I 1 I507del 1 L206W 1 365insT 1 3272-26A>G 1 3272-26A/G 1 E585X 1 2789þ5G>A 1 L15P 1 2752-15C>G 1 G576Aa 1 R347H 1 R334Q 1 R668Ca 1 2689insG 1 R347H 1 CFTRdele2,3 1 R1070W 1 E831X 1 L1227S 1 I 1027T 1 R1070W 1 E831X 1 3272-26A>G 1 L997F 1 I853F 1 A349V 1 6T 1 Note: CFTR ¼ cystic fibrosis transmembrane conductance regulator. Login to comment

PMID: 20657600 [PubMed] Giuliani R et al: "Identification of the second CFTR mutation in patients with congenital bilateral absence of vas deferens undergoing ART protocols."

No. Sentence Comment

58 INNO-LiPA CFTR19 INNO-LiPA CFTR17 INNO-LiPA CFTR Italian regional [delta]F508 621+1G>T 1259insA G542X 3849+10kbC>T 4016insT N1303K 2183AA>G 4382delA W1282X 394delTT 852del22 G551D 2789+5G> A R1162X D579G 1717-1G>A 3659delC G1244E R553X R117H G1349D CFTRdele2,3 (21 kb) R334W I502T [delta]I507 R347P L1065P 711+1G>T G85E R1158X 3272-26A>G 3905insT 1078delT T338I R560T A455E S549R(A>C) 1898+1G>A S1251N 2143delA 711+5G>A 991del5 I148T E60X D1152H 3199del6 3120+1G>A 2184delA 1898+3A>G, R1070Q Q552X Poli-T tract variations R1066H R347H 621+3A>G R334Q E217G Abbreviation: CFTR, cystic fibrosis transmembrane conductance regulator. Login to comment

PMID: 9922375 [PubMed] Sheppard DN et al: "Structure and function of the CFTR chloride channel."

No. Sentence Comment

98 These residues are conserved across spe- because I0 blocks the pore, it appears that I0 is less per- cies, and two are the site of mutations associated with meable under some conditions, including the whole cell CF: R334Q/W and R347C/H/L/P (142). Login to comment

PMID: 17440499 [PubMed] Keymolen K et al: "Clinical outcome of preimplantation genetic diagnosis for cystic fibrosis: the Brussels' experience."

No. Sentence Comment

66 Table 1 Assessment of CF risk Couples with PGD (n ¼ 47) Couples without PGD (n ¼ 22) All couples (n ¼ 69)(%) CF risk assessment Affected child or foetus 23 14 37 (53.6) CBAVD (without other CF complaints) 7 3 10 (14.5) During fertility work-up (not CBAVD) 10 10 (14.5) Positive family history 3 2 5 (7.2) CF patient (with CBAVD in males) 4 4 (5.8) Unknown 2 2 (2.9) Preconceptual screening 1 1 (1.4) Table 2 Reasons for choosing PGD Couples with PGD (n ¼ 47) Couples without PGD (n ¼ 22) All couples (n ¼ 69) Reason for choosing/informing about PGD Fertility problems 24 7 31 (44.9%) Objection to abortion 15 2 17 (24.6%) History of termination of pregnancy 8 1 9 (13%) Unknown 11 11 (15.9%) Other 1 1 (1.4%) Table 3 Genotypes of the couples with PGD cycles Female partner Male partner Number of couples with this genotype p.F508del/- p.F508del/- 17 p.F508del/- p.R117H/- (7T/9T) 1 p.2789+5G4A/- p.D110H/p.D110H 1 p.G542X/- p.F508del/- 1 p.R334Q/- p.F508del/- 1 p.R553X/- p.F508del/- 2 p.1717-1G4A p.2183AA4G/5T 1 p.F508del/- p.F508del/? Login to comment

PMID: 22612315 [PubMed] Li MS et al: "Pseudohalide anions reveal a novel extracellular site for potentiators to increase CFTR function."

No. Sentence Comment

37 In some experiments, additional mutations (R334Q, K892Q, R899Q) were introduced into this background using the QuikChange site-directed mutagenesis system. Login to comment
104 Examples of the macroscopic I-V relationships for R334Q, K892Q, R899Q and K892Q/R899Q (all in an E1371Q background) are shown in Figure 5A. Login to comment
105 Apparent block in intact cells was weak in R334Q and was not significantly weakened further by inclusion of 10 mM Co(CN)6 3- (Figure 5D) or Co(NO2)6 3- (Figure 5E) in the pipette solution. Login to comment
113 Each of these mutants (R334Q, K892Q, R899Q, K892Q/R899Q) also abolished the sensitivity of current inhibition in intact cells to extracellular Cl- ions (Figure 6). Login to comment
207 This suggestion of a non-pore-mediated effect is further strengthened by the effects of mutations that remove positive charges from the extracellular face of the CFTR protein. Thus the R334Q mutant, which neutralizes a pore lining positive charge that is known to attract extracellular anions into the outer mouth of the pore (Smith et al., 2001; Gong and Linsdell, 2003c; Zhou et al., 2007), did affect the ability of Co(CN)6 3- and Co(NO2)6 3- to weaken apparent channel block in intact cells (Figures 5, 7). Login to comment
208 However, this apparent lack of pseudohalide sensitivity in R334Q appears to reflect weak cytoplasmic block under control conditions rather than a specific loss of external anion sensitivity of block (Figure 7). Login to comment
209 This interpretation is consistent with the R334Q mutation itself affecting cytoplasmic blocker interactions with CFTR (Zhou et al., 2007). Login to comment

PMID: 15130785 [PubMed] Gong X et al: "Maximization of the rate of chloride conduction in the CFTR channel pore by ion-ion interactions."

No. Sentence Comment

35 Results and discussion Previously we characterized the properties of six different R334 mutants (R334C, R334E, R334H, R334K, R334L, and R334Q) [19]. Login to comment
66 R334Q, and (,) R334W. Login to comment
98 Interestingly, three of these mutations-R334L, R334Q, and R334W-have been identified in cystic fibrosis patients [29]. Login to comment

PMID: 19448737 [PubMed] Zhou JJ et al: "Evidence that extracellular anions interact with a site outside the CFTR chloride channel pore to modify channel properties."

No. Sentence Comment

38 Consistent with this distinction, we previously showed that the R334Q mutation at the outer mouth of the pore disrupted interactions between external Cl- and internal Pt(NO2)4 2-, without affecting interactions between external Pt(NO2)4 2- and internal Pt(NO2)4 2- (Zhou et al. 2007). Login to comment
67 Similar weakening of block by internal Pt(NO2)4 2-was also observed in K114C, K329A, K335A, and R1128Q (Fig. 2), as well as R334Q (Zhou et al. 2007). Login to comment
127 The effects of external Pt(NO2)4 2are sensitive to mutations away from the pore (K892Q, R899Q) but not deep within the pore (K335A, R334Q), which would be expected to alter ion-ion interactions in the pore. Login to comment

PMID: 24727426 [PubMed] Wang Y et al: "Understanding how cystic fibrosis mutations disrupt CFTR function: from single molecules to animal models."

No. Sentence Comment

2002 Mutation of R334, including the CF mutations R334L and R334Q, transformed the current-voltage (I-V) relationship of CFTR from linear (or quasi-linear, see Cai et al., 2003) to strongly inwardly rectifying (Smith et al., 2001; Gong and Linsdell, 2003). Login to comment

PMID: 25277268 [PubMed] Broadbent SD et al: "The cystic fibrosis transmembrane conductance regulator is an extracellular chloride sensor."

No. Sentence Comment

112 To explore the role of phosphorylation further, we studied the effect of deleting the R domain from CFTR (residues 634-836) [12, 7], which removes all the major PKA/PKC Table 1 Summary of the FSK stimulation of whole cell currents and Erev shifts observed with the CFTR constructs used in this study CFTR Construct n FSK Stimulation (%&#b1;SEM) Erev shift (mV&#b1;SEM) WT (50 bc;M ATP) 5 180&#b1;96 15.0&#b1;3.6 WT (100 bc;M ATP) 6 12,000&#b1;6,000 15.2&#b1;3.0 WT (300 bc;M ATP) 8 1,200&#b1;600 17.0&#b1;3.0 WT (1 mM ATP) 24 13,000&#b1;6,000 23.7&#b1;1.8 WT (1.3 mM ATP) 9 1,400&#b1;900 16.7&#b1;2.6 WT (2 mM ATP) 24 6,100&#b1;5,300 16.7&#b1;1.6 WT (5 mM ATP) 7 1,600&#b1;1,000 20.1&#b1;4.4 WT (50 bc;M ATP + 50 bc;M P-ATP) 7 224&#b1;130 15.3&#b1;1.0 WT + Genistein 4 7,600&#b1;5,200 26.1&#b1;5.4 WT + AMP-PNP 5 2,800&#b1;2,500 21.8&#b1;5.5 WT (3 mM MgCl2) 7 28,000&#b1;17,000 18.3&#b1;3.1 R104Q 5 4,600&#b1;1,600 28.6&#b1;4.7 K114C 5 12,000&#b1;6,700 29.2&#b1;3.0 R117Q 4 33,000&#b1;20,000 30.1&#b1;3.4 K329A 5 13,000&#b1;10,000 33.7&#b1;2.1 R334Q 9 13,000&#b1;6,700 27.3&#b1;2.9 K335A 5 3,200&#b1;1,500 20.8&#b1;7.1 W401G 7 2,600&#b1;1,800 18.5&#b1;4.8 Delta-R (No Stim) 5 - 25.1&#b1;2.7 Delta-R (No FSK, Genistein) 5 140&#b1;13 22.7&#b1;3.0 Delta-R (FSK, No Genistein) 4 89&#b1;14 15.6&#b1;6.0 Delta-R (FSK + Genistein) 6 639&#b1;432 25.1&#b1;4.9 Delta-R-E1371S (No FSK) 9 - 21.4&#b1;4.8 Delta-R-E1371S (FSK) 4 2,600&#b1;1,400 15.3&#b1;4.7 K892Q 7 16,000&#b1;9,500 36.8&#b1;4.8 R899E 4 1,200&#b1;400 25.0&#b1;2.7 R899K 4 1,600&#b1;900 26.6&#b1;2.9 R899Q 7 5,400&#b1;2,800 30.0&#b1;1.3 R899Q + AMP-PNP 4 72,000&#b1;50,000 15.2&#b1;2.8 R899Q-E1371Q (No FSK) 4 - 18.4&#b1;5.9 R899Q-E1371Q (FSK) 6 107&#b1;48 15.6&#b1;3.0 R1128Q 6 14,000&#b1;6,100 41.1&#b1;4.2 Y1219G 6 3,200&#b1;2,500 19.2&#b1;3.3 E1371Q (No FSK) 6 - 25.5&#b1;3.5 E1371Q (FSK) 8 -28&#b1;9 22.3&#b1;4.0 E1371Q (FSK, No ATP, No GTP) 8 270&#b1;130 19.4&#b1;4.5 E1371Q + AMP-PNP (No FSK) 4 - 24.7&#b1;6.5 E1371Q + AMP-PNP (FSK) 8 180&#b1;170 17.4&#b1;4.0 Vector Control 4 15&#b1;38 - FSK stimulation was calculated as the percentage increase in current density at -60 mV from the Erev, after 5-min exposure to 10 bc;M FSK. Login to comment
162 In support of this conclusion, the stimulating effect of [Cl- ]o cannot be due to the ion entering the pore, since mutations that do affect CFTR Cl-conductance (R104Q, R117Q, R334Q, K335A) have no effect on [Cl- ]o stimulation (Fig. 2), and the one site that is important for sensing (R899) does not affect Cl-conductance [45, 47]. Login to comment

PMID: 25892339 [PubMed] Linsdell P et al: "Interactions between permeant and blocking anions inside the CFTR chloride channel pore."

No. Sentence Comment

6 However, the I344K mutation does not increase single channel conductance following disruption of Cl-binding in the outer vestibule in R334Q channels. Login to comment
105 Consistent with this model, neutralization of this charge in the R334Q/E1371Q mutant abolished the relationship between intracellular Pt(NO2)4 2- block and extracellular [Cl- ] (Fig. 6A-D). Login to comment
106 Block under low [Cl- ] conditions was weakened by the R334Q mutation (Table 1; also compare results for R334Q/E1371Q in Fig. 6C with E1371Q in Fig. 2D), resulting in a significant increase in Pt KD at all voltages (P b 0.002). Login to comment
108 The R334Q mutation also appeared to increase the voltage-dependence of block (Table 1), although the reasons for this effect are not clear. Login to comment
109 Since the R334Q and I344K mutations in different parts of the pore (Fig. 1) had opposite effects on the [Cl- ]o-sensitivity of Pt(NO2)4 2- block - which was practically abolished in R334Q/E1371Q (Fig. 6) but greatly increased in I344K/E1371Q (Figs. 4, 5) - these mutations were combined to generate a R334Q/I344K/E1371Q mutant. Login to comment
110 Not only did R334Q/I344K/E1371Q channels exhibit strong Pt(NO2)4 2- block (Table 1), but block was also strongly dependent on extracellular [Cl- ] (Fig. 6E-H). Login to comment
111 This confirms that the I344K mutation not only strengthens interactions with intracellular Pt(NO2)4 2- ions but also with extracellular Cl-ions. Furthermore, this effect on interactions with extracellular Cl- appears independent of the presence of a positively charged side chain at position 334: whereas the R334Q mutation abolishes Cl- -dependence of block in E1371Q channels (Fig. 6D), it does not in I344K- bearing E1371Q channels (Fig. 6H). Login to comment
112 Thus, interactions with external Cl- that are lost in R334Q/E1371Q channels are at least partially restored by the I344K mutation. Login to comment
113 To examine if the I344K mutation also resulted in altered interactions with other extracellular anions - and if this effect was also independent of R334 -Pt(NO2)4 2- block was also investigated with other extracellular anions, both in I344K/E1371Q and in R334Q/I344K/ E1371Q channels (Fig. 7). Login to comment
117 Secondly, formate was able to significantly increase Pt KD(0) relative to gluconate in both I344K/E1371Q (Fig. 7G) and in R334Q/I344K/E1371Q (Fig. 7H), unlike in E1371Q where formate had no significant effect (Fig. 3D, E). Login to comment
128 Pt KD(0) (4 mM Cl- ) (bc;M) zb4; (4 mM Cl- ) Pt KD(0) (154 mM Cl- ) (bc;M) zb4; (154 mM Cl- ) E1371Q 183.7 &#b1; 33.2 (9) -0.397 &#b1; 0.030 (9) 441.0 &#b1; 28.6 (7) -0.503 &#b1; 0.026 (7) R899Q/E1371Q 189.9 &#b1; 55.0 (6) -0.362 &#b1; 0.063 (6) 434.0 &#b1; 32.2 (7) -0.458 &#b1; 0.048 (7) K95Q/E1371Q 1110 &#b1; 172 (6)** -0.244 &#b1; 0.022 (6)* 1422 &#b1; 218 (6)** -0.193 &#b1; 0.041 (6)** I344K/E1371Q 6.92 &#b1; 1.48 (6)** -1.589 &#b1; 0.125 (6)** 164.7 &#b1; 27.5 (7)** -1.604 &#b1; 0.080 (7)** R334Q/E1371Q 1081 &#b1; 220 (4)** -0.637 &#b1; 0.106 (4)* 1112 &#b1; 144 (4)** -0.621 &#b1; 0.051 (4)* R334Q/I344K/E1371Q 39.24 &#b1; 7.94 (4)* -1.093 &#b1; 0.037 (4)** 258.3 &#b1; 30.7 (5)* -1.075 &#b1; 0.033 (5)** Fig. 4. Effect of mutations that weaken or strengthen intracellular Pt(NO2)4 2- block. Login to comment
150 External Cl- -dependence of Pt(NO2)4 2- block is abolished in R334Q/ E1371Q (Fig. 6C, D; Fig. 10A), consistent with the positive charge at this site in the outer vestibule of the pore (Fig. 1) being crucial for interactions between the channel and extracellular Cl-ions that are required for ion:ion interactions inside the pore [33,43]. Login to comment
151 Binding of Pt(NO2)4 2- ions to R334Q/E1371Q was somewhat weaker than E1371Q (Fig. 10C; Table 2), consistent with earlier reports that mutations at R334 disrupt blocker binding in the pore inner vestibule, perhaps by a long-range conformational effect on the pore [56]. Login to comment
152 The voltage-dependence of Pt(NO2)4 2-binding is also increased in R334Q/E1371Q (Fig. 10C). Login to comment
153 However, the very low apparent Cl- affinity of R334Q/E1371Q implied by the apparent [Cl- ]-independence of Pt KD in this mutant (Figs. 6D, 10A) precluded quantitative analysis of Pt Kocc(0) and Cl K in this case; the lack of slope illustrated in the relationships in Figs. 6D and 10A imply extremely low Cl-binding affinity, consistent with ablation of the external Cl-binding site. Login to comment
154 Although the R334Q mutant abolished Cl- -dependence of Pt(NO2)4 2- block, the double pore mutant R334Q/I344K/E1371Q showed strongly Cl- -dependent block (Fig. 6E-H; Fig. 10B), suggesting that the presence of the I344K mutant restores Cl-binding that is lost in R334Q/E1371Q. Login to comment
155 Quantitative analysis of data from R334Q/I344K/ E1371Q (Fig. 10; Table 2) suggests that the presence of the second fixed positive charge in the inner vestibule at position 344 still supports strong Pt(NO2)4 2-binding (Fig. 10C), although (as for E1371Q) Pt(NO2)4 2-binding is somewhat weakened by the R334Q mutation (Fig. 10C). Login to comment
156 Binding of Pt(NO2)4 2-to Cl- -occupied channels is similar in R334Q/E1371Q and R334Q/I344K/E1371Q (Fig. 10D), suggesting that R334 plays little or no role in ion:ion interactions in mutant channels bearing a positive charge at position 344. Login to comment
157 Chloride binding also remains strong in R334Q/I344K/E1371Q, although it too is somewhat weakened by the R334Q mutation (Fig. 10E). Login to comment
158 The strong effect of external Clon Pt(NO2)4 2-binding to R334Q/I344K/E1371Q channels is illustrated in Fig. 9D. Login to comment
168 (A, B, E, F) Example macroscopic I-V relationships for R334Q/E1371Q (A, B) or R334Q/I344K/E1371Q (E, F) under high (154 mM; A, E) or low (4 mM; B, F) extracellular [Cl- ] conditions. In each case currents were recorded before (control) and after the addition of Pt(NO2)4 2- (at the concentrations indicated) to the intracellular solution. Login to comment
172 There was no significant difference in these parameters for R334Q/E1371Q (E) (P N 0.5). Login to comment
178 These interactions may be important for maximization of single channel conductance (see Introduction), as exemplified by the very low conductance observed for R334Q and for other substitutions at this site [33]. Login to comment
179 However, the reduced single channel conductance observed in R334Q channels (Fig. 12) was not significantly rescued by the I344K mutation (Fig. 12). Login to comment
183 (A, B) Example macroscopic I-V relationships for I344K/E1371Q (A) or R334Q/I344K/E1371Q (B) with extracellular solution containing 150 mM SCN- . Login to comment
221 Because of the lack of [Cl- ]o-dependence in R334Q/E1371Q, values for Pt Kocc, Pt zb4;occ, Cl K and Cl zb4; could not be obtained for this mutant. Login to comment
222 Pt Kvac(0) (bc;M) Pt zb4;vac Pt Kocc(0) (bc;M) Pt zb4;occ Cl K (mM) Cl zb4; E1371Q 245 -0.39 1440 -0.63 179 +0.22 K95Q/E1371Q 1150 -0.23 4400 -0.58 296 +0.20 I344K/E1371Q 0.174 -0.42 978 -1.12 0.264 +1.09 R334Q/E1371Q 1120 -0.71 - - - - R334Q/I344K/E1371Q 31.8 -1.04 1500 -1.15 232 +0.23 Fig. 9. Effect of bound extracellular Cl-ions on the binding of intracellular Pt(NO2)4 2- ions. Login to comment
233 Indeed, the R334Q mutation significantly decreases Pt(NO2)4 2-binding affinity (Fig. 10C; Table 1). Login to comment
241 Analysis of Pt(NO2)4 2- and Cl-binding to channel variants containing the R334Q mutation. Login to comment
242 (A, B) Effect of extracellular [Cl- ] ([Cl- ]o) on the measured Pt KD in R334Q/E1371Q (A) and R334Q/I344K/E1371Q (B) at different membrane potentials as indicated. Login to comment
246 Note that, because of the apparent lack of effect of external Clon Pt(NO2)4 2- block in R334Q/ E1371Q, it was not possible to obtain values for Pt Kocc or Cl K for this mutant. Login to comment
266 However, the R334Q mutation has only a minor impact on Cl-binding in the presence of I344K, and Cl-binding to the R334Q/I344K/E1371Q mutant remains strong and strongly voltage-dependent (Fig. 10; Table 2). Login to comment
268 Indeed, knock-off of Pt(NO2)4 2- by Cl- appears similar in I344K/ E1371Q and R334Q/I344K/E1371Q channels (Fig. 10D), suggesting that anion binding near R334 plays little role in ion:ion interactions that occur in channels bearing the I344K mutation. Login to comment
271 The apparent anion selectivity of the external anion binding site is also slightly altered in I344K-containing channels (Fig. 7G, H), and this appears independent of the presence or absence of the R334Q mutation. Login to comment
275 Single channel conductance of R334Q-containing channels. Login to comment
276 (A) Example single-channel currents recorded at a membrane potential of -60 mV for the wild type, R334Q, and R334Q/I344K channels as indicated. Login to comment
282 strengthoftheinteractionbetweenthem,isalteredinI344K-containingchan- nels.Thus,thedestabilizingeffectofCl- onPt(NO2)4 2-binding-evaluated fromthedifferencebetweenPt(NO2)4 2- bindinginvacantandCl- -occupied channels(i.e.betweenPt KvacandPt Kocc)-ismuchgreaterinI344K/E1371Q (and to a lesser extent R334Q/I344K/E1371Q) than in E1371Q or K95Q/ E1371Q(Fig.9).Strengthenedinteractionsbetweenboundanionsarealso suggestedbytheincreasedapparentcouplingbetweenthemovementof Pt(NO2)4 2- andCl- ionsinsidetheporeinI344K(Fig.8E). Login to comment
287 These different mechanisms are illustrated in wild type (A, C) and R334Q/I344K channels (B, D) that are proposed to isolate the two different mechanisms of ion:ion interaction; it is presumed that both mechanisms are active in I344K (and neither in R334Q). Login to comment
289 (B) In R334Q/I344K channels, Cl- does not bind to the outer pore mouth, but instead binds further into the pore from its extracellular end (experiencing a greater fraction of the transmembrane electric field) and binds close to the introduced lysine in the inner vestibule, where it strongly antagonizes Pt(NO2)4 2-binding (leading to very strong [Cl- ]o-dependence of block). Login to comment
291 (D) In R334Q/I344K, even if multiple Cl-ions are able to bind close together in the inner vestibule, this does not result in rapid Cl-permeation in the absence of Cl-binding to the outer pore region. Login to comment
297 In effect, in the R334Q/I344K double pore mutant, one kind of antagonistic Cl- :blocker interaction (Fig. 13A) has been replaced by another with a different molecular mechanism (Fig. 13B). Login to comment
312 However, although I344K appears capable of restoring sensitivity to external Cl-ions that is lost in R334Q, this does not result in a significant restoration of unitary Cl-conductance (Fig. 12). Login to comment
313 In other words, although it is suggested that in R334Q/I344K channels one form of knock-off inside the pore has been replaced by another (Fig. 13B), this surrogate knock-off mechanism does not appear to be capable of supporting high Cl-conductance in the way that normal ion-ion interactions in wild type CFTR are proposed to do (Fig. 13C, D). Login to comment

PMID: 26493493 [PubMed] Destouni A et al: "Single-cell high resolution melting analysis: A novel, generic, pre-implantation genetic diagnosis (PGD) method applied to cystic fibrosis (HRMA CF-PGD)."

No. Sentence Comment

79 Validation case no. Genotype combination (HGVS CFTR reference sequences NM000492.3 and NG016465.1) Light scanner (LSC) exons (Montgomery et al. 2007) Number of cells tested Amplicons in multiplex RxNa PCR efficiency (%) Overall ADO (%) 1 p.Arg334Gln and c.489+3ANG 7.2 and 4.2 48 8 98.85% 2% 2 p.Phe508del and p.Leu732X 10 and 13.3 60 8 98% 1.66% 3 p.Phe508del and p.Asp110His 10 and 4.1 60 8 96.60% 3.33% 4 p.Phe508del and p.Gly542X 10 and 11 40 8 98% 3% Total lymphocytes tested 208 a RxN: reaction, ADO: allele drop-out 3 The mutation p.Phe508del could otherwise more rapidly be detected by fluorescent fragment analysis by incorporating the relevant primer set in the first PCR. Login to comment
101 PGD case no. Genotype combination (HGVS CFTR reference sequences NM000492.3 and NG016465.1) LSC exons (legacy nomenclature) (Montgomery et al., 2007) No. of blastomeres received for diagnosis No. of blastomeres amplified No. of blastomeres genotyped No. of unaffected blastomeres Pregnancy Confirmation of PGD result by PNDa 1 p.Arg334Gln and c.489+3ANG 7.2 and 4.2 5 4 4 2 No N/A 2 p.Phe508del and p.Phe508del 10 11 10 10 6 Yes Yes 3 p.Phe508del and c.489+1GNT 10 and 4.2 8 7 7 4 Yes Yes 4 p.Phe508del and p.Leu732X 10 and 13.3 10 8 8 5 Yes Yes 5 p.Phe508del and p.Asp1152His 10 and 18 4 3 3 3 Yes Yes 6 p.Phe508del and c.2051_2052delAAinsG 10 and 13.2 5 4 4 3 Yes Yes 7 p.Phe508del and p.Gly1069Arg 10 and 17bA1 9 9 9 4 Yes No (BP) 8 p.Phe508del and p.Gly542X 10 and 11 3 3 3 2 Yes Yes 9 p.Phe508del and c.3140-26ANG 10 and 17bA1 8 8 7 3 No N/A 10 p.Gly542X and p.Gly542X 11 2 2 2 1 No transfer 11 p.Glu826Lys and p.Phe508del 13.4 and 10 6 6 4 3 Yes Miscarried 12 p.D1312G and c.489+1GNT 21 and 4.2 11 9 9 8 Yes Miscarried 13 p.Glu279Asp and p.Phe508del 6b and 10 7 7 5 3 No N/A 14 p.Phe508del and p.Gly1069Arg 10 and 17bA1 9 8 8 5 Yes No (BP) 15 p.Glu822X and p.Gly1069Arg 13.4 and 17bA1 5 5 5 5 Yesb Miscarried Total 103 93 88 57 N/A: non-applicable, BP: biochemical pregnancy. Login to comment