ABCMdb

ABCC7 p.Thr665Ser

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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

112 Jewish 1) 405+1G®A (48.0%) 3) W1282X (17.0%) - - 4 23 Kerem et al. [1995] (Tunisia) 2) DF508 (31.0%) 4) 3849+10KbC®T (4.0%) Jewish 1) G85E 4) G542X - - 6 10 Kerem et al. [1995] (Turkey) 2) DF508 5) 3849+10KbC®T 3) W1282X 6) W1089X Jewish (Yemen) None - - 0 5 Kerem et al. [1995] Lebanon 1) DF508 (35.0%) 6) 4096-28G®A (2.5%) - - 9 40 Desgeorges et al. [1997] 2) W1282X (20.0%) 7) 2789+5G®A (2.5%) 3) 4010del4 (10.0%) 8) M952I (2.5%) 4) N1303K (10.0%) 9) E672del (2.5%) 5) S4X (5.0%) Reunion ∆F508 (52.0%) 1717-1G→A (0.7%) 90.4 81.7 9 138 Cartault et al. [1996] Island Y122X (24.0%) G542X (0.7%) 3120+1G→A (8.0%) A309G (0.7%) A455E (2.2%) 2789+5G→A (0.7%) G551D (1.4%) Saudi North: 3) H139L - - North 1 49 families El-Harith et al. [1997]; Arabia 1) 1548delG 4) L1177X Central 3 Kambouris et al. [1997]; Central: 5) DF508 South 4 Banjar et al. [1999] 1)I1234V 6) 3120+1G®A West 9 2)1548delG 7) 425del42 East 6 3)DF508 8) R553X South: 9) N1303K 1) I1234V East: 2) 1548delG 1) 3120+1G®A 3) 711+1G®T 2) H139L 4) 3120+1G®A 3) 1548delG West: 4) DF508 1) I1234V 5) S549R 2) G115X 6) N1303K Tunisia ∆F508 (17.6%) G85E (2.6%) 58.7 34.5 11 78 Messaoud et al. [1996] G542X (8.9%) W1282X (2.6%) 711+1G→T (7.7%) Y122X (1.3%) N1303K (6.4%) T665S (1.3%) 2766del8NT (6.4%) R47W+D1270N (1.3%) R1066C (2.6%) Turkeye ∆F508 (24.5%) 1066L (1.3%) 80.6 65.0 36 1067/670 Yilmaz et al. [1995]; Estivill et al. 1677delTA (4.1%) E822X (1.3%) [1997]; Onay et al. [1998]; 2789+5G→A (3.9%) 2183+5G→A+2184insA (1.3%) Macek et al. [2002] 2181delA (3.8%) D110H (0.8%) R347H (3.6%) P1013L (0.8%) N1303K (2.9%) 3172delAC (0.8%) 621+1G→T (2.6%) 1259insA (0.8%) G542X (2.6%) M1028I (0.8%) TABLE 1. Continued. Estimated Projected detection of Number of Number of Country/ allele two CFTR mutations chromosomes Region Mutation array detectiona mutationsb includedc (max/min)d Reference WORLDWIDEANALYSISOFCFTRMUTATIONS587 E92K (2.6%) 4005+1G→A (0.7%) A96E (2.6%) W1282X (0.7%) M152V (2.6%) I148T (0.6%) 2183AA→G (2.5%) R1162X (0.6%) 296+9A→T (1.6%) D1152H (0.6%) 2043delG (1.4%) W1098X (0.6%) E92X (1.4%) E831X (0.6%) K68N (1.4%) W496X (0.6%) G85E (1.3%) F1052V (0.5%) R1158X (1.3%) L571S (0.5%) United Arab S549R (61.5%) ∆F508 (26.9%) 88.4 78.1 2 86/52 Frossard et al. [1988]; Emirates Frossard et al. [1999] North/Central/South Americas Argentina ∆F508 (58.6%) N1303K (1.8%) 69.1 47.7 5 326/228 CFGAC [1994]; Chertkoff et al. W1282X (3.9%) 1717-1G→A (0.9%) [1997] G542X (3.9%) Brazilf ∆F508 (47.7%) W1282X (1.3%) 66.8 44.6 10 820/500 CFGAC [1994]; Cabello et al. (total) G542X (7.2%) G85E (1.3%) [1999]; Raskin et al. [1999]; R1162X (2.5%) R553X (0.7%) Bernardino et al. [2000] R334W (2.5%) L206W (0.6%) N1303K (2.4%) 2347delG (0.6%) South East: >∆F508, G542X South: >N1303K Brazil ∆F508 (31.7%) N1303K (2.5%) 42.5 18.1 3 120 Parizotto and Bertuzzo [1997] (Sao Paulo) G542X (8.3%) Canada ∆F508 (59.0%) G542X (0.5%) 98.5 97.0 13 381/200 Rozen et al. [1992]; (Lac St. Jean) 621+1G→T (24.3%) N1303K (0.5%) De Braekeleer et al. [1998] A445E (8.2%) Q890X (0.5%) Y1092X (1.2%) S489X (0.5) 711+1G→T (1.0%) R117C (0.5%) I148T (1.0%) R1158 (0.5%) G85E (0.8%) Canada ∆F508 (71.4%) ∆I507 (1.3%) 90.9 82.6 7 77 Rozen et al. [1992] (Quebec City) 711+1G→T (9.1%) Y1092X (1.3%) 621+1G→T (5.2%) N1303K (1.3%) A455E (1.3%) Canada ∆F508 (70.9%) W1282X (0.9%) 82.0 67.2 10 632 Kristidis et al. [1992] (Toronto) G551D (3.1%) R117H (0.9%) G542X (2.2%) 1717-1G→A (0.6%) 621+1G→T (1.3%) R560T (0.6%) N1303K (0.9%) ∆I507 (0.6%) Chile ∆F508 (29.2%) R553X (4.2%) 33.4 11.2 2 72 Rios et al. [1994] Columbia 1) DF508 (35.4%) 3) N1303K (2.1%) - - 4 48 Restrepo et al. [2000] 2) G542X (6.3%) 4) W1282X (2.1%) Ecuador 1) DF508 (25%) - - 1 20 Paz-y-Mino et al. [1999] (Continued) BOBADILLAETAL. Login to comment

PMID: 12913074 [PubMed] Aznarez I et al: "Characterization of disease-associated mutations affecting an exonic splicing enhancer and two cryptic splice sites in exon 13 of the cystic fibrosis transmembrane conductance regulator gene."

No. Sentence Comment

3 We have also determined whether five other CF mutations D648V, D651N, G654S, E664X and T665S located near this putative ESE could lead to aberrant splicing of exon 13. Login to comment
5 In addition, we have shown that D648V, E664X and T665S mutations could cause aberrant splicing of exon 13 by improving the polypyrimidine tracts of two cryptic 30 splice sites. Login to comment
130 Both the E664X and T665S mutations were found to cause an increase in the D248 transcript (Fig. 3C, lanes 2 and 5, respectively) by 2and 5-fold, respectively (Fig. 3E). Login to comment
134 3C and E) added further support to the conclusion that E664X and T665S could cause skipping of the first 248 nucleotides of exon 13 by improving the polypyrimidine tract of the 248-cryptic 30 splice site. Login to comment
144 We next investigated the effect of co-transfection of an expression plasmid for SF2/ASF with the minigene reporters containing the D651N, E664X and T665S mutations. Login to comment
163 (C) RT-PCR analysis of COS-7 cell lines transfected with minigenes driven by the CMV promoter carrying the wild-type exon 13 sequence, WT, and E664X, 2123A!T, 2124G!T, T665S, 2123AGA!TTT, 2123A!G/2125A!G and 2126C!A mutations separated in a 2% agarose gel. Login to comment
176 We have also expanded the search for other relevant sequences to the splicing of exon 13 and analyzed the effect of five additional previously reported CFTR mutations, D648V, D651N, G654S, E664X and T665S. Login to comment
177 The aberrant splicing of exon 13 observed for D648V, E664X and T665S mutations is probably due to strengthening the polypyrimidine tract adjacent to one of two cryptic 30 splice sites, located at 195 and 248 nt, downstream of the native 30 splice site. Login to comment
181 For example, the molecular consequence of D648V and T665S was previously predicted to cause amino acid changes that could affect the chloride channel activity of the CFTR. Login to comment
183 However, from the present study, we predict that the CF phenotype associated with the D648V and T665S mutations is most likely due to their effect on exon 13 splicing. Login to comment
203 Minigenes carrying D651N, E664X and T665S mutations were transfected alone (noted by the minus sign) or co-transfected with SF2/ASF (noted by the plus sign). Login to comment
212 Conversely, SF2/ASF exacerbated the effect of D651N, E664X and T665S mutations on the splicing of exon 13. Login to comment
221 The mutations were reported to associate with CF phenotype [D648V (31), E656X (http:// www.genet.sickkids.on.ca/cftr/), 2108delA (27), E664X (33) and T665S (http://www.genet.sickkids.on.ca/cftr/)] or with pulmonary disease [D651N (32)]. Login to comment

PMID: 12940920 [PubMed] Rowntree RK et al: "The phenotypic consequences of CFTR mutations."

No. Sentence Comment

79 Furthermore, mutants T665S and E826K showed no difference from the wild-type channel conductance. Login to comment

PMID: 9736778 [PubMed] Vankeerberghen A et al: "Characterization of 19 disease-associated missense mutations in the regulatory domain of the cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

9 Finally, T665S and E826K CFTR had single channel properties not significantly different from wild-type CFTR. Login to comment
68 Primers used for mutagenesis Primer Sequence I601F (a1933t) 5'-CTA ACA AAA CTA GGT TTT TGG TCA CTT C-3' L610S (t1961c) 5'-CTA AAA TGG AAC ATT CAA AGA AAG CTG-3' A613T (g1969a) 5'-CAT TTA AAG AAA ACT GAC AAA ATA TTA-3' D614G (a1973g) 5'-CAT TTA AAG AAA GCT GGC AAA ATA TTA A-3' I618T (t1985c) 5'-GAC AAA ATA TTA ACT TTG CAT GAA GG-3' L619S (t1988c) 5'-GAC AAA ATA TTA ATT TCG CAT GAA GGT-3' H620P (a1991c) 5'-CAA AAT ATT AAT TTT GCC TGA AGG TAG C-3' H620Q (t1992g) 5'-AAT ATT AAT TTT GCA GGA AGG TAG CAG-3' G622D (g1997a) 5'-TTG CAT GAA GAT AGC AGC TAT TTT TAT G-3' G628R (g2014c) 5'-GCA GCT ATT TTT ATC GGA CAT TTT C-3' L633P (t2030c) 5'-CAT TTT CAG AAC CCC AAA ATC TAC AGC-3' D648V (a2075t) 5'-CTC ATG GGA TGT GTT TCT TTC GAC C-3' T665S (a2125t) 5'-CAA TCC TAA CTG AGT CCT TAC ACC G-3' F693L (t2209c) 5'-CAG ACT GGA GAG CTT GGG GAA AAA AG-3' R766M (g2429t) 5'-GCA CGA AGG ATG CAG TCT GTC CTG-3' R792G (c2506g) 5'-CAG CAT CCA CAG GAA AAG TGT CAC TG-3' A800G (c2531g) 5'-CTG GCC CCT CAG GGA AAC TTG ACT G-3' I807M (a2553g) 5'-CTG AAC TGG ATA TGT ATT CAA GAA GG-3' E822K (g2596a) 5'-GGC TTG GAA ATA AGT AAA GAA ATT AAC G-3' E826K (g2608a) 5'-GAA GAA ATT AAC AAA GAA GAC TTA AAG-3' Selection primer BstBI 5'-CTC TGG GGT CCG GAA TGA CCG AC-3' Two primers were used for each mutagenesis reaction. Login to comment
77 Mutations detected in patients (I601F, L610S, A613T, D614G, I618T, L619S, H620P, H620Q, D622G, G628R, L633P, T665S, F693L, K698R, V754M, R766M, R792G, A800G, I807M, E822K and E826K) are indicated in bold and underlined, the PKA phosphorylation sites by an arrow and the two acidic domains are boxed. Login to comment
83 Four mutations (T665S, R792G, E822K and E826K) caused a significant reduction in the cAMP-induced chloride current. Login to comment
87 Maturation pattern of RD mutations and their associated phenotype found in patients with the indicated genotype (when the mutation is associated with CF, only the pancreas status is given) Mutation A-form B-form C-form Clinical data Genotype Phenotype Reference I601F + + - I601F/G542X PS M. Schwarz, personal communication L610S + + - Unknown Unknown A613T + + - Unknown Unknown D614G + + - D614G/unknown PI 14 I618T + + - I618T/dF508 PS G.R. Cutting, personal communication L619S + + - L619S/unknown PI B. Tümmler, personal communication H620P + + - H620P/R1158X PS M. Schwarz, personal communication H620Q + + + H620Q/dF508 PI T. Dörk, personal communication G622D + + + G622D/unknown Oligospermia J. Zielenski, personal communication G628R + + - Unknown Unknown L633P + + - L633P/3659delC M. Schwarz, personal communication D648V + + + D648V/3849+10kb C/T PI C. Ferec, personal communication T665S + + + Unknown Unknown F693L + + + F693L/W1282X Healthy C. Ferec; CF Genetic Analysis Consortium R766M + + + R766M/R792G CBAVD D. Glavac, personal communication R792G + + + R766M/R792G CBAVD D. Glavac, personal communication A800G + + + A800G/unknown CBAVD 34 I807M + + + I807M/unknown CBAVD Our observation E822K + + + E822K/unknown PI 35 E826K + + + E826K/unknown Thoracic sarcoidosis C. Bombieri, personal communication +, the protein matures up to that form; -, the protein does not reach the respective maturation step. Login to comment
123 Mutations that did not affect maturation (H620Q, G622D, D648V, T665S, F693L, R766M, R792G, A800G, I807M, E822K and E826K) were subsequently analysedat theelectrophysiologi- cal level. Login to comment
131 The remaining mutations (D648V, T665S, F693L, R766M, I807M and E826K) caused no significant alterations in intrinsic chloride channel activity. Login to comment

PMID: 17572159 [PubMed] Loumi O et al: "CFTR mutations in the Algerian population."

No. Sentence Comment

16 Still, 3 mutations may be specific to the Algerian [7-9] population (A141D, L227R, and N1303H) and 2 to the Tunisian population (T665S and 2766del8). Login to comment

PMID: 9175873 [PubMed] Annereau JP et al: "A novel model for the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

70 The maturation patterns of six mutant R domain proteins were determined (Fig. 3): CFTR-L610S, CFTR-G628R and CFTR-L633P matured to the core-glycosylated form, while CFTR-D648V, CFTR-T665S and CFTR-R766M matured to the complete glycosylated form. Login to comment
150 The mutations L610S (tc at 1961), G628R (gc at 2014), L633P (tc at 2030), D648V (at at 2075), T665S (at at 2125) and R766M (gt at 2429) (nucleotide and amino acid assignment according to [2]) were introduced using the Transformer Site-Directed Mutagenesis kit (Clontech, Heidelberg, Germany). Login to comment
151 The mutations L610S (tc at 1961), G628R (gc at 2014), L633P (tc at 2030), D648V (at at 2075), T665S (at at 2125) and R766M (gt at 2429) (nucleotide and amino acid assignment according to [2]) were introduced using the Transformer Site-Directed Mutagenesis kit (Clontech, Heidelberg, Germany). Login to comment

PMID: 11001817 [PubMed] Chen JM et al: "Definition of a "functional R domain" of the cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

30 Second, while I601F, L610S, A613T, D614G, I618T, L619S, H620P, G628R, and L633P resulted in aberrant processing, neither D648V or T665S caused an arrest in protein maturation (8). Login to comment

PMID: 16837250 [PubMed] Naguib ML et al: "Cystic fibrosis detection in high-risk Egyptian children and CFTR mutation analysis."

No. Sentence Comment

103 Table 2 Clinical findings and mutation analysis of the cystic fibrosis patients Patient number Consanguineous marriage Affected sibling Age (y) Sex Clinical findings Sequence analysis Sweat chloride (mmol/L) 3 Y N 1.5 M Jaundice, FTT 1540A>G (M470V)/unidentified 100 10 Y N 1.1 M PULM, GI, FTT 2125A>T (T665S)/unidentified 90 13 Y N 0.2 F PULM, GI, FTT N/A 120 17 Y N 0.5 M PULM, FTT N/A 95 20 Y N 0.7 M PULM, FTT N/A 90 22 Y Y 2.5 F PULM, FTT ƊF508/ƊF508 96 23 N N 0.5 F PULM, FTT 1898+3A>C/4041G>C (N1303K) 97 41 Y Y 0.5 F PULM, GI, FTT 1540A>G (M470V)/unidentified 85 46 Y N 2 M PULM, FTT Unidentified/unidentified 90 55 N Y 0.7 M PULM, GI, FTT ƊF508/unidentified 80 58 Y N 0.6 M PULM, FTT N/A N/A 22/B Ìe; Y Y 7 M PULM, GI, FTT ƊF508/ƊF508 N/A 1540A>G (M470V): a sequence variant which is a common polymorphism in the CFTR gene. Login to comment
114 One patient was identified as a carrier of the 2125A>T (T665S) missense mutation in exon 13a. Login to comment

PMID: 23378595 [PubMed] Tsui LC et al: "The cystic fibrosis gene: a molecular genetic perspective."

No. Sentence Comment

105 Other examples of mutations affecting splicing efficiency include several missense (D648V and T665S) and nonsense(E664X)mutations,presumablyduetothe disruption of the ESE elements within exon 13 (Aznarez et al. 2003). Login to comment

PMID: 25735457 [PubMed] Ramalho AS et al: "Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations."

No. Sentence Comment

31 Indeed, it was demonstrated that several CFTR missense mutations also alter splicing, e.g., p.Asp565Gly and p.Gly576Ala [20], p.Asp648Val and p.Thr665Ser [21] as well as p.Gly893Gly (c.2811 G N T) [22]. Login to comment