ABCMdb

ABCC7 p.Asp565Gly

[switch to full view]
Comments [show]

None has been submitted yet.

Publications

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

50 Mutation D565G had previously been reported in a CBAVD patient (Kanavakis et al. 1998). 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
81 Two patients had two mutations each (F508del and I1027T; D565G and R668C). Login to comment
83 Mutation D565G is a novel Greek mutation previously reported by us in a CBAVD patient (Kanavakis et al. 1998). Login to comment

PMID: 11810271 [PubMed] Tzetis M et al: "Qualitative and quantitative analysis of mRNA associated with four putative splicing mutations (621+3A-->G, 2751+2T-->A, 296+1G-->C, 1717-9T-->C-D565G) and one nonsense mutation (E822X) in the CFTR gene."

No. Sentence Comment

1 We studied four subjects with 621+3A→G, two with 2751+2T→A, one with 296+1G→C, two with 1717-9T→C-D565G and seven with E822X and compared the results with CFTR mRNA from normal subjects. Login to comment
2 Our results showed that mutations 621+3A→G, 2751+2T→A, and 296+1G→C, which disrupt the 5` splice donor sites of introns 4, 14a, and 2, respectively, and 1717-9T→C-D565G, which possibly disrupts the exonic splicing enhancer sequences of exon 12 (owing to the missense mutation in cis), lead to the production of aberrantly spliced mRNA in nasal epithelial cells. Login to comment
5 The complex allele 1717-9T→C-D565G results in aberrant splicing of CFTR mRNA with production of transcripts lacking exon 12 (major product), with minor amounts of transcripts revealing joint exon 11 and 12 skipping. Login to comment
19 Ultimately, however, all the disease-causing mutations result in defective cAMP-regulated Cl-secretion by epithelial cells, though for various reasons, namely defective pro- Maria Tzetis · Alexandra Efthymiadou · Stavros Doudounakis · Emmanuel Kanavakis Qualitative and quantitative analysis of mRNA associated with four putative splicing mutations (621+3A→G, 2751+2T→A, 296+1G→C, 1717-9T→C-D565G) and one nonsense mutation (E822X) in the CFTR gene Hum Genet (2001) 109:592-601 DOI 10.1007/s00439-001-0631-0 Received: 18 June 2001 / Accepted: 13 September 2001 / Published online: 6 November 2001 ORIGINAL INVESTIGATION M. Tzetis · A. Efthymiadou · E. Kanavakis (✉) Department of Medical Genetics, Athens University, "Aghia Sophia" Children`s Hospital, Thivon & Livadias, Athens, 11527, Greece e-mail: ekanavak@cc.uoa.gr, Tel.: +30-1-7467460, Fax: +30-1-7795553 S. Doudounakis Cystic Fibrosis Unit, "Aghia Sophia" Children`s Hospital, Athens, Greece (c) Springer-Verlag 2001 tein production (class I), defective protein processing (class II), defective regulation (class III), defective conduction (class IV), or defective synthesis (class V) (Welsh and Smith 1993; Zielenski and Tsui 1995). Login to comment
30 We have investigated three putative splicing mutations, 621+3A→G, 2751+2T→A, 296+1G→C, which disrupt the 5` splice donor sites of introns 4, 14a, and 2, respectively, and the complex allele 1717-9T→C-D565G, which should disrupt the 3` acceptor splice site of intron 10 and possibly cause skipping of exon 12 owing to missense mutation D565G. Login to comment
36 Patients and controls Nasal epithelial cells were collected from four subjects with 621+3A→G (all compound heterozygotes), two with 2751+2T→A (one compound heterozygote and one carrier), one with 296+1G→C, two with 1717-9T→C-D565G (both only carriers), and seven with E822X (three compound heterozygotes, two homozygotes, and two carriers). Login to comment
37 A patient with the 621+1G→T mutation and one with the 1898+1G→T were also studied for the appropriate cDNA fragment and the results were compared with those of mutations 621+3A→G and D565G, respectively. Login to comment
59 593 594 Table1Genotype/phenotypeoftheCFTRpatientsa DevelopmentPulmonaryfunctionCFTRgenotypeAge (yrs) SexAgeat diagnosis Sweattest (mEq/l) Meconium ileusHeight (%-ile) Weight (%-ile) Pancreatic status FEV1 (%) FVC (%) Other Bacterial pathogens Other clinical features F508del/621+3AÆÆÆÆG6FBirth108.5Yes<50%>50%PI10398-Sa,Klebsiella- F508del/621+3AÆÆÆÆG7M2mos93.6No>10%~25%PI131132-Sa,Hi,Sa- 1898+1GÆÆÆÆT/621+3AÆÆÆÆG18F3mos82.1No>97%<90%PI7370Bronchi- ectasis Sa,PaDiabetes W1282X/621+3AÆÆÆÆG2F8mos100.9No<75%>75%PI---Hi,Psputida- F508del/2751+2TÆÆÆÆA5MBirth85.7Yes75%75%PI---Sa,Pa- 3120+1GÆA/296+1GÆÆÆÆC33M27yrs93.1No>75%~50%PI133128-Pa- 1717-9TÆÆÆÆC-D565G/Nb 7F5yrs41.4No??PS? Login to comment
91 C Sequencing results of alternatively spliced transcript (253 bp), lacking all of exon 4 1717-9T→C-D565G cDNA from nasal epithelial cells of two heterozygotes with 1717-9T→C-D565G, two controls, and a patient with the 1898+1G→T mutation was amplified with primers F2/B21 spanning exons 10 to 13. Login to comment
100 Discussion Analysis of CFTR mRNA from nasal epithelial cells, which are the cells biologically relevant to the disease process in CF, shows that mutations 621+3A→G, 2751+2T→A, 296+1G→C, and double allele 1717-9T→C-D565G result in the production of aberrantly spliced mRNA transcripts and that nonsense mutation E822X results in severe reduction of CFTR mRNA. Login to comment
111 The reduc- 598 Fig.3A-D mRNA results for mutations 296+1G→C and 1717-9T→C-D565G. Login to comment
113 A mRNA RT-PCR products analysed by 2% agarose gel electrophoresis. M, Marker lane, phiX174/HaeIII DNA; lane 1: normal control; lane 2: sample with mutation 296+1G→T. B mRNA RT-PCR products analysed by 2% agarose gel electrophoresis. M, Marker lane, phiX174/HaeIII DNA; lanes 1 and 2: samples with double allele 1717-9T→C-D565G; lane 3: sample with mutation 1898+1G→T; lane 4: normal control. Login to comment
129 Two aberrantly spliced transcripts were produced by double allele 1717-9T→C-D565G (mRNA transcripts lacking exon 12 as a major product and a minor aberrant transcript lacking both exons 11 and 12), while mutation 1818+1G→T produced aberrant transcripts lacking exon 12 only. Login to comment
133 However, the high percentage of aberrant transcripts produced lacking exon 12, comparable to those produced from the 1818+1G→T, which is a true splicing mutation, could be the result of D565G (A→G@1826). Login to comment
141 Further studies are needed in order to confirm the effect of D565G mutation on such sequences in exon 12. Login to comment
147 In conclusion, the splicing mutations (621+3A→G, 2751+2T→A, 296+1G→C, and 1717-9T→C-D565G) all lead to the production of alternatively spliced CFTR transcripts. Login to comment

PMID: 12200467 [PubMed] Vrettou C et al: "Multiplex sequence variation detection throughout the CFTR gene appropriate for preimplantation genetic diagnosis in populations with heterogeneity of cystic fibrosis mutations."

No. Sentence Comment

24 cells PCR ADO/total polymorphism (length bp) amplified product (%) cells (%) Patient 1 F508del 25 (196) 10 50 47 (94.0) 0/47 (0) 621 ϩ 1G→T 23 (192) 4 48 (96.0) 1/48 (2.1) Patient 2 N1303K 25 (196) 21 85 80 (94.1) 3/80 (3.8) 2789 ϩ 5G→A 18 (182) 14b 85 (100) 2/85 (2.4) Patient 3 E822X 17 (180) 13 part b 80 72 (90.0) 1/72 (1.4) F1052V 18 (182) 17b 75 (93.8) 2/75 (2.6) Heterozygotea 1719-9T→C 17 (180) 11 75 75 (100.0) 0/75 (0) R668C 13 part a Normal allele 18 (182) 74 (98.7) 1/74 (1.4) Microsatellite 290 268 (92.4) 29/268 (10.8) IVS8CA aIndividual heterozygote for D565G mutation in exon 12 (not included in assay) had two polymorphisms in cis to D565G (1719-9T→C in exon 11 and R668C in exon 13 part a), which were also in cis with 17 CA repeats in IVS8. Login to comment

PMID: 12719375 [PubMed] Pagani F et al: "New type of disease causing mutations: the example of the composite exonic regulatory elements of splicing in CFTR exon 12."

No. Sentence Comment

4 This is the case in both natural mutations D565G and G576A (the latter having previously considered a neutral polymorphism) and several site-directed silent substitutions. Login to comment
29 This is the case for two interesting and enigmatic missense mutations, D565G and G576A. Login to comment
30 The D565G mutation was previously reported in a young subject during a screening program and suspected of inducing exon skipping (19). Login to comment
38 Mutations inducing exon skipping include both missense D565G and G576A mutants and several neutral substitutions. Login to comment
40 RESULTS D565G and G576A missense mutations cause CFTR exon 12 skipping in vivo We evaluated, in nasal epithelial cells, the pattern of CFTR exon 12 splicing in both normal subjects and heterozygous individuals with D565G and G576A alleles. Login to comment
41 The missense D565G mutation was detected in seven Greek subjects, always in cis with the common polymorphism R668C (2134C/T) in exon 13 (Table 1). Login to comment
46 Two PCR`s were set up for the nasal epithelial cell cDNA derived from each of the D565G and G576A heterozygotes and from heterozygous controls for R668C, using the common F3 forward primer in exon 11 and each of the two allele specific primers of exon 13 (Fig. 1A). Login to comment
48 In heterozygous individuals the 668C allele carrying the mutations D565G or G576A clearly showed a significantly lower proportion of normal transcripts containing exon 12 than the 668R allele (Fig. 1B, lanes 7-20). Login to comment
53 This analysis showed that the mutant D565G and G576A alleles produced about 40 and 22% of exon inclusion, respectively (Table 1). Login to comment
54 These results indicate that, in nasal epithelial cells, the D565G and G576A missense mutations cause a splicing defect affecting the recognition of CFTR exon 12. Login to comment
55 Defective CFTR exon 12 recognition in hybrid minigenes containing D565G and G576A missense mutations In order to study in more detail the splicing regulation of CFTR exon 12 we have developed a faithful splicing assay that mimics the in vivo situation. Login to comment
61 Allele-specific PCR transcript analysis F3/668R F3/668C Subjects with D565G mutation 89.7Æ 5.9 40Æ 8.3a Subject with G576A mutation 88Æ 3 22Æ 4b Normal controls (heterozygotes for polymorphism R668C) 91.7Æ 5.1 89.3Æ 8.1 Data from six subjects with the D565G mutation, one patient with the G576A mutation and four controls are calculated from the experimental proportions of CFTR exon 12 inclusion adjusted according to the graph shown in Figure 1C. Login to comment
63 a Transcripts containing exon 12 derived from the D565G allele. b Transcripts containing exon 12 derived from the G576A allele. Login to comment
65 RT-PCR allele-specific amplification experiments in D565G and G576A carriers. Login to comment
67 The position of the missense substitutions (D565G and G576A) in exon 12 and of the C668R polymorphic variant in exon 13 is indicated. Login to comment
70 The D565G and G576A carriers presented the missense mutation in cis with the 668C variant. Login to comment
72 RNA extracted from nasal epithelial cells from R688C heterozygous controls (lanes 1-6), from D565G carriers (lanes 7-18) and from the G576A carrier (lanes 19-20), was reverse transcribed and amplified with F3/668C primers (even-numbered lanes) and with F3/668R primers (odd-numbered lanes). Login to comment
89 We then studied the pattern of splicing of a minigene with the missense mutations D565G, G576A and Y577F, the latter associated to classical CF. Login to comment
90 The D565G showed about 35% of normal transcripts containing exon 12 (Fig. 2C). Login to comment
93 This indicates that, unlike G565A and D565G, the disease-causing effect of Y577F cannot be attributed to a splicing abnormality but rather to a protein defect. Login to comment
94 These results indicate that the two missense D565G and G576A mutations associated with non-classical CF induce variable proportion of exon 12 skipping, with G576A most severely affected. Login to comment
97 To evaluate their role in CFTR exon 12 we transfected normal and the three D565G, G576A and Y577F minigenes in different cell lines (Fig. 3A). Login to comment
98 For each cell line tested, the three variants cause comparable changes in splicing efficiency, with D565G and G576A inducing exon skipping and Y577F exon inclusion. Login to comment
118 In WTB, D565G and G576A, overexpression of any of the two splicing factors caused an increase in CFTR exon 12 skipping. Login to comment
119 The amount of normal transcript containing the exon 12 were reduced in WTB (40-51%), very low in D565G (7-12%) and virtually absent in the G576A mutant (Fig. 3B). Login to comment
121 These results indicate that, in the presence of high concentration of inhibitory splicing factors, the D565G and G576A missense mutations produce very low levels of normal CFTR transcripts. Login to comment
124 A total number of 26 hybrid minigenes were analysed containing site-directed mutations at two target sequences of the exon: the AAGATGC sequence at the 50 end from position 12 to 18, which includes D565G at position 15, and a central GGATAC sequence from position 47 to 52 which contains G576A and Y577F of position 48 and 51, respectively (Fig. 4). Login to comment
156 The mild CF phenotypes of the D565G and G576A patients may be explained considering that the variant CFTR protein is functional and that the defect is the consequence of exon 12 skipping induced by the nucleotide change. Login to comment
162 Thus, according to tissue concentration of regulatory splicing factors, and their variations from individual to individual, the D565G and G576A may produce different quantities of mRNAs lacking the exon leading to phenotype variability. Login to comment
187 MATERIALS AND METHODS Patients and DNA mutation analysis Nasal epithelial cells were collected from six individuals carriers of mutation D565G (A>G at 1826 in CFTR cDNA), from one CBAVD patient with G576A and from four non-CF control individuals heterozygotes for the polymorphism R668C. Login to comment
189 Clinical data and CFTR genotypes of all the D565G and G576A carriers are shown in Table 2. Login to comment
193 The phase of linkage for missense mutations D565G and G556A and polymorphism R668C was deduced from family studies and confirmed by sequencing of allele specific cDNAs. Login to comment
225 Data on individual carriers of D565G and G576A mutations Patient code CFTR genotypea Age (years) Sex Reason for CF testing Sweat test (mEq/l) Pancreatic status 1PM D565G/À 16 F Nasal polyposis, Sa 65, 70 PS 2DF D565G 7 1717À9T>C/À 7 F Recurrent episodes of pneumonia 41.4 PS 3MA D565G/À Adult M Carrier status nt nt 4KA D565G/À Adult F Carrier status nt nt 5KP D565G/À Adult M Carrier status nt nt 6PRA D565G/À Adult F Carrier status nt nt 7ORAb D565G/À Adult M CBAVD <40 PS 8 G576A/À Adult M Testicular azoospermia nt nt PS, pancreatic sufficiency; Sa, Staphylococcus; nt, non-tested; CBAVD, congenital bilateral absence of vas deferens. Login to comment

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

No. Sentence Comment

132 Additionally, point mutations that are assumed to be single nucleotide polymorphisms (SNPs) play a role in CF disease by interfering with splicing signals (see aberrant splicing of exon 9) and causing mis-splicing of the gene, such as 1717-9T → C-D565G in exon 12 (Tzetis et al. 2001), as reviewed by Cartegni et al. 2002. Login to comment

PMID: 15472711 [PubMed] Nissim-Rafinia M et al: "Restoration of the cystic fibrosis transmembrane conductance regulator function by splicing modulation."

No. Sentence Comment

13 The second group includes mutations that generate both aberrantly and correctly spliced transcripts (such as 3849 þ 10 kb C-T, 3272À26 A-G, IVS8-5T, D565G and G576A), the level of which varies among patients and among organs of the same patient (Ramalho et al, 2002; Pagani et al, 2003; reviewed in Nissim-Rafinia & Kerem, 2002). 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
59 T, 1811 þ 1.6 kb A >G, 3272 À 26A !G, IVS8-5T, D565G, G576A, c4006 À 1 G À> A, 2789 þ 5 G > A 1 Included are mutations that have been studied in RNA/protein level or having enough experimental data to suggest their molecular mechanism. Login to comment
234 CLASS V MUTATIONS: REDUCED NUMBER OF ACTIVE CFTR This group includes mutations which generate both aberrantly and correctly spliced transcripts (such as 3849 þ 10 kb C -> T, 3272 À 26 A -> G, IVS8-5T, D565G, and G576A), the levels of which vary among different patients and among different organs of the same patient.85-89 These patients often have a relatively mild phenotype, yet with variable disease expression, from minimal lung disease, pancreatic sufficiency, and male fertility to relatively severe disease with multiorgan involvement.88,89 This variable disease expression is inversely correlated with the level of correctly spliced transcripts, such that lower levels are associated with a severe disease, while higher levels are associated with a milder phenotype. Login to comment

PMID: 16088537 [PubMed] Luisetti M et al: "Genetics of idiopathic disseminated bronchiectasis."

No. Sentence Comment

42 Greek M/F 11/12 5/16 na Mean age (yrs) 53 Ϯ 15 53 Ϯ 14 na CFTR gene 1 G576A-R668C/L997F 1 ⌬F508/D192N 1 ⌬F508,I1027T mutation 1 ⌬F508/L997F 1 ⌬I507/3849 + 10kb C → T 1 D565G, R668C 1 ⌬F508/- 1 ⌬F508/3849 + 10kb C → T 1 T896I/- 1 R1066C/- 1 H949Y/T1220I 1 I148T/- 1 3667ins4/- 1 ⌬F508/- 1 ⌬F508/S977F 1 R75Q/- 1 2183AA→G 1 M1137V/- 1 L997F/- IVS8-5T 5 5/7 1 5/9 1 5/5 CFTR, cystic fibrosis transmembrane conductance regulator; na, not available. 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: 19893581 [PubMed] Forzan M et al: "Is CFTR 621+3 A>G a cystic fibrosis causing mutation?"

No. Sentence Comment

103 4 Tzetis, M., Efthymiadou, A., Doudounakis, S. & Kanavakis, E. Qualitative and quantitative analysis of mRNA associated with four putative splicing mutations (621+3A4G, 2751+2T-4A, 296+1G-4C, 1717-9T-4C-D565G) and one nonsense mutation (E822X) in the CFTR gene. Login to comment

PMID: 9620832 [PubMed] Kanavakis E et al: "Cystic fibrosis mutation screening in CBAVD patients and men with obstructive azoospermia or severe oligozoospermia."

No. Sentence Comment

55 Results The analysis of the entire coding sequence identified 12 different molecular defects including ∆F508, and two are novel defects (D565G and 2790-8CϾG) (Table I). Login to comment
56 Of the two novel mutations, one was identified in a CBAVD case and is a missence mutation D565G, the other is a possible splicing defect 2790-8CϾG and was detected in a male with obstructive azoospermia. Login to comment
64 Cystic fibrosis transmembrane conductance regulator (CFTR), PolyT genotypes and clinical data of men with congenital bilateral absence of the vas deferens (CBAVD, n ϭ 14), obstructive azoospermia (ObsA, n ϭ 10) and oligozoospermia (n ϭ 3) Patients Sweat chloride CFTR IVS8-polyT Other clinical (mEq/l) mutations alleles features Two mutations detected MS1 (CBAVD) 107.7 ∆F508/M1I 5T/9T Recurrent bronchitis MS6 (CBAVD) 74.5 ∆F508/711ϩ3AϾG 9T/7T Chronic cough MS19 (CBAVD) 51 W496X/F1052V 9T/9T MS24 (CBAVD) Ͻ40 D565G/R668C 7T/7T One mutation detected MS5 (CBAVD) Ͻ40 3272-26AϾG/- 7T/7T MS12 (CBAVD) Ͻ40 ∆F508/- 9T/7T MS14 (CBAVD) Ͻ40 ∆F508/- 9T/5T MS15 (CBAVD) 57.7 L732X/- 7T/5T Dehydration/recurrent bronchitis MS16 (CBAVD) Ͻ40 711ϩ3AϾG/- 7T/5T MS20 (CBAVD) Ͻ40 4010delTAT/- 7T/7T MS18 (ObsA) 48 ∆F508/- 5T/9T MS11 (ObsA) Ͻ40 R75Q/- 7T/7T MS23 (ObsA) Ͻ40 2790-8CϾG/- 7T/7T No mutation detected MS7 (CBAVD) Ͻ40 -/- 7T/7T MS10 (CBAVD) Ͻ40 -/- 7T/7T MS21 (CBAVD) Ͻ40 -/- 7T/9T MS28 (CBAVD) Ͻ40 -/- 7T/7T MS2 (ObsA) 54.2 -/- 7T/7T MS8 (ObsA) Ͻ40 -/- 7T/7T MS17 (ObsA) 50 -/- 7T/7T MS22 (ObsA) Ͻ40 -/- 7T/9T MS25 (ObsA) Ͻ40 -/- 7T/7T MS26 (ObsA) Ͻ40 - / - 7T/7T MS27 (ObsA) Ͻ40 -/- 7T/7T MS3 (oligozoospermia) 50 -/- 7T/7T MS4 (oligozoospermia) Ͻ40 -/- 7T/7T MS13 (oligozoospermia) Ͻ40 -/- 7T/7T Table II. Login to comment
81 No mutation, except for ∆F508, was prevalent in individuals in this study and all of the mutations found in the CBAVD patients, except for the novel D565G and mutation R668C, have also been found in Greek CF patients (Tzetis et al., 1977). Login to comment
82 The novel missence mutation D565G has not been detected in Ͼ250 CF chromosomes, nor in Ͼ100 non-CF chromosomes that we have examined. Login to comment
83 The substitution produced by mutation D565G involves a change of a positively charged for a polar uncharged amino acid in exon 12 of the gene. Login to comment

PMID: 15241793 [PubMed] Steiner B et al: "The role of common single-nucleotide polymorphisms on exon 9 and exon 12 skipping in nonmutated CFTR alleles."

No. Sentence Comment

184 Sequence variations (i.e., p.D565G and p.G576A) in the newly identified composite exonic regulatory element of splicing (CERES) of exon 12 [Pagani et al., 2003b] were excluded by SSCP and sequence analysis. Login to comment

PMID: 15463919 [PubMed] Amaral MD et al: "Quantitative methods for the analysis of CFTR transcripts/splicing variants."

No. Sentence Comment

164 D565G, G576A and Y577Y induce exon skipping, while Y577F increases the percentage of exon 12 inclusion. Login to comment
169 In particular, two missense mutations, D565G and G576A (previously considered a neutral polymorphism), showed no clear association with loss of protein function or disease phenotype. Login to comment
173 D565G and G576A induce variable levels of exon 12 skipping, thus reducing levels of normal transcripts. Login to comment

PMID: 12068373 [PubMed] Hefferon TW et al: "Atypical 5' splice sites cause CFTR exon 9 to be vulnerable to skipping."

No. Sentence Comment

237 Hum Mol Genet 6:85-90 Tzetis M, Efthymiadou A, Doudounakis S, Kanavakis E (2001) Qualitative and quantitative analysis of mRNA associated with four putative splicing mutations (621ϩ3ArG, 2751ϩ2TrA, 296ϩ1GrC, 1717-9TrC- D565G) and one nonsense mutation (E822X) in the CFTR gene. Login to comment
238 Hum Mol Genet 6:85-90 Tzetis M, Efthymiadou A, Doudounakis S, Kanavakis E (2001) Qualitative and quantitative analysis of mRNA associated with four putative splicing mutations (621af9;3ArG, 2751af9;2TrA, 296af9;1GrC, 1717afa;9TrCafa; D565G) and one nonsense mutation (E822X) in the CFTR gene. Login to comment

PMID: 24685677 [PubMed] Pranke IM et al: "Biosynthesis of cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

1376 These splicing mutations (e.g. 3849 + 10 kb C ࢐ T, 3272-26 A ࢐ G, IVS8-5T, D565G and G576A) lead to variable levels of correctly spliced transcripts among different patients and among different organs of the same patient. 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