ABCMdb

PMID: 17662673

Alibakhshi R, Kianishirazi R, Cassiman JJ, Zamani M, Cuppens H
Analysis of the CFTR gene in Iranian cystic fibrosis patients: identification of eight novel mutations.
J Cyst Fibros. 2008 Mar;7(2):102-9. Epub 2007 Jul 27., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC7 p.Trp1145Arg The CBAVD patient was found to be homozygous for the p.W1145R mutation. Login to comment 8 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Ser466* ABCC7 p.Ser466* The most common mutations were p.F508del (ΔF508) (18.1%), c.2183_2184delAAinsG (2183AANG) (6.5%), p.S466X (5.8%), p.N1303K (4.3%), c.2789+5GNA (4.3%), p.G542X (3.6%), c.3120+1GNA (3.6%), p.R334W (2.9%) and c.3130delA (2.9%). Login to comment 10 ABCC7 p.Trp1145Arg ABCC7 p.Thr1036Ile ABCC7 p.Ala566Asp Eight mutations, c.406-8TNC, p.A566D, c.2576delA, c.2752-1_2756delGGTGGCinsTTG, p.T1036I, p.W1145R, c.3850-24GNA, c.1342-?_1524+?del, were found for the first time in this study. Login to comment 14 ABCC7 p.Trp1145Arg ABCC7 p.Thr1036Ile ABCC7 p.Ala566Asp Keywords: Cystic fibrosis; CFTR; Mutations; Iran; Direct sequencing; c.2576delA; p.A566D; c.2752-1_2756delGGTGGCinsTTG; p.T1036I; p.W1145R; CFTRdele9; c.406-8TNC; c.3850-24GNA 1. Login to comment 27 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* A few mutations, such as p.F508del, p.N1303K and p.G542X, are frequent worldwide. Login to comment 36 ABCC7 p.Lys68Glu ABCC7 p.Lys68Glu of chromosomes p.K68E E3 A to G at 334 Lys to Glu at 68 1 c.406-8TNC I3 T to C at 406-8 mRNA splicing defect? Login to comment 37 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1066Cys ABCC7 p.Arg1066Cys ABCC7 p.Arg1066Cys ABCC7 p.Arg1066Cys ABCC7 p.Ser945Leu ABCC7 p.Ser945Leu ABCC7 p.Ser945Leu ABCC7 p.Ser945Leu ABCC7 p.Arg170His ABCC7 p.Arg170His ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro ABCC7 p.Lys1177* ABCC7 p.Lys1177* ABCC7 p.Asp192Gly ABCC7 p.Asp192Gly ABCC7 p.Thr1086Ile ABCC7 p.Thr1086Ile ABCC7 p.Thr1086Ile ABCC7 p.Thr1086Ile ABCC7 p.Arg785* ABCC7 p.Arg785* ABCC7 p.Thr1036Ile ABCC7 p.Thr1036Ile ABCC7 p.Thr1036Ile ABCC7 p.Thr1036Ile ABCC7 p.Ala566Asp ABCC7 p.Ala566Asp 1 c.406-3TNC I3 T to C at 406-3 mRNA splicing defect 1 p.R170H E5 G to A at 641 Arg to His at 170 1 p.D192G E5 A to G at 707 Asp to Gly at 192 2 p.R334W E7 C to T at 1132 Arg to Trp at 334 4 c.1525-1GNA I9 G to A at 1525-1 mRNA splicing defect 2 p.F508del E10 Deletion of CTT from 1653 Deletion of Phe at 508 25 p.S466X E10 C to G at 1529 Ser to stop at 466 8 c.1677delTA E10 Deletion of TA from 1677 Frame shift 2 p.G542X E11 G to T at 1756 Gly to stop at 542 5 p.S549R E11 T to G at 1779 Ser to Arg at 549 2 p.A566D E12 C to A at 1829 Ala to Asp at 566 2 c.1898+1GNT I12 G→T at 1898+1 mRNA splicing defect 2 c.2183_2184delAAinsG E13 A to G at 2183 and deletion of A at 2184 Frame shift 9 c.2576delA E13 Deletion of A at 2576 Frame shift 1 c.2043delG E13 Deletion of A at 2043 Frame shift 1 c.2184insA E13 Insertion of A after 2184 Frame shift 1 p.R785X E13 C to T at 2485 Arg to stop at 785 2 c.2752-1_2756delGGTGGCinsTTG I14a/ Deletion of GGTGGC mRNA splicing defect 2 E14b From 2752-1 to 2756 and insertion TTG c.2789+5GNA I14b G to A at 2789+5 mRNA splicing defect 6 p.S945L E15 C to Tat 2966 Ser to Leu at 945 2 c.3120+1GNA I16 G to A at 3120+1 mRNA splicing defect 5 c.3121-1GNA I16 G to A at 3121-1 mRNA splicing defect 2 c.3130delA E17a Deletion of A at 3130 Frame shift 4 p.T1036I E17a C to T at 3239 Thr to Ile at 1036 1 p.R1066C E17b C to T at 3328 Arg to Cys at 1066 1 p.L1077P E17b T to C at 3362 Leu to Pro at 1077 1 p.T1086I E17b C to T at 3389 Thr to Ile at 1086 1 p.R1162X E19 C to T at 3616 Arg to stop at 1162 2 p.K1177X E19 A to T at 3361 Lys to stop at 1177 2 c.3850-24GNA I19 G to A at 3850-24 mRNA splicing defect? Login to comment 38 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Ser1455* 1 p.N1303K E21 C to G at 4041 Asn to Lys at 1303 6 p.S1455X E24 C to G at 4496 Ser to stop at 1455 1 c.186-?_296+?del E2 Large in frame deletion starting in intron 1, ending in intron 2 1 c.1342-?_1524+?del E9 Large in frame deletion starting in intron 8, ending in intron 9 1 c.406-?_1716+?del E4-E10 Large in frame deletion starting in intron 3, ending in intron 10 2 Mutations described for the first time appear in bold. Login to comment 50 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg560Thr Mutations were detected as follows: In a first phase, all subjects were analyzed with an amplification refractory mutation system assay (ARMS-PCR), as described by Ferrie et al. [20], detecting the following mutations: p.F508del, p.N1303K, p.G542X, c.1717-1GNA, p.R553X, p.W1282X, p.G551D, c.621+1GNT, c.I507del and p.R560T. Login to comment 65 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ser549Arg ABCC7 p.Ser549Arg ABCC7 p.Ser1455* ABCC7 p.Arg1066Cys ABCC7 p.Ser945Leu ABCC7 p.Ser945Leu ABCC7 p.Leu1077Pro ABCC7 p.Lys1177* ABCC7 p.Lys1177* ABCC7 p.Asp192Gly ABCC7 p.Asp192Gly ABCC7 p.Ser466* ABCC7 p.Ser466* ABCC7 p.Thr1086Ile ABCC7 p.Arg785* ABCC7 p.Arg785* ABCC7 p.Thr1036Ile ABCC7 p.Ala566Asp ABCC7 p.Ala566Asp Results A total of 69 unrelated CF patients (38 male and 31 female; aged between 2 months and 15 years) of Iranian Table 2 Genotype of CFTR genes in 53 Iranian patients Genotype Exon/intron Number of patients p.F508del/p.F508del E10/E10 10 p.F508del/p.R1162X E10/E19 2 p.F508del/p.T1036I E10/E17a 1 p.F508del/p.R1066C E10/E17b 1 p.F508del/c.1342-?_1524+?del E10/E9 1 p.S466X/p.S466X E10/E10 4 c.2183_2184delAAinsG/ c.2183_2184delAAinsG E13/E13 4 c.2183_2184delAAinsG/c.186- ?_296+?del E13/E2 1 p.N1303K/p.N1303K E21/E21 2 p.N1303K/p.S945L E21/E15 1 p.N1303K/c.1677delTA E21/E10 1 p.G542X/p.G542X E11/E11 2 p.G542X/c.2789+5GNA E11/I14b 1 c.3120+1GNA/c.3120+1GNA I16/I16 2 c.3120+1GNA/c.3121-1GNA I16 1 c.3121-1GNA/p.T1086I I16/E17b 1 c.3130delA/c.3130delA E17a/E17a 2 p.D192G/p.D192G E5/E5 1 p.R334W/p.R334W E7/E7 1 p.R334W/p.S945L E7/E15 1 p.R334W/p.L1077P E7/E17b 1 c.1525-1GNA/c.1525-1GNA I9/I9 1 p.S549R/p.S549R E11/E11 1 p.A566D/p.A566D E12/E12 1 c.1898+1GNT/c.1898+1GNT I12/I12 1 c.2576delA/p.S1455X/ E13/E24 1 c.2184insA/c.1677delTA E10/E13 1 p.R785X/p.R785X E13/E13 1 c.2752-1_2756delGGTGGCinsTTG/ c.2752-1_2756delGGTGGCinsTTG I14a/E14b 1 c.2789+5GNA/c.2789+5GNA I14b/I14b 1 p.K1177X/p.K1177X E19/E19 1 c.406-?_1716+?del/c.406-?_1716+?del E4-E10/E4-E10 1 Total 53 origin were extensively studied for the presence of mutations in the CFTR gene, for the presence of the deep intronic 3849+10 kbC࢐T mutation, and large deletions/ duplications. Login to comment 66 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ser549Arg ABCC7 p.Ser549Arg ABCC7 p.Ser1455* ABCC7 p.Arg1066Cys ABCC7 p.Ser945Leu ABCC7 p.Ser945Leu ABCC7 p.Leu1077Pro ABCC7 p.Lys1177* ABCC7 p.Lys1177* ABCC7 p.Asp192Gly ABCC7 p.Asp192Gly ABCC7 p.Ser466* ABCC7 p.Ser466* ABCC7 p.Thr1086Ile ABCC7 p.Arg785* ABCC7 p.Arg785* ABCC7 p.Thr1036Ile ABCC7 p.Ala566Asp ABCC7 p.Ala566Asp Results A total of 69 unrelated CF patients (38 male and 31 female; aged between 2 months and 15 years) of Iranian Table 2 Genotype of CFTR genes in 53 Iranian patients Genotype Exon/intron Number of patients p.F508del/p.F508del E10/E10 10 p.F508del/p.R1162X E10/E19 2 p.F508del/p.T1036I E10/E17a 1 p.F508del/p.R1066C E10/E17b 1 p.F508del/c.1342-?_1524+?del E10/E9 1 p.S466X/p.S466X E10/E10 4 c.2183_2184delAAinsG/ c.2183_2184delAAinsG E13/E13 4 c.2183_2184delAAinsG/c.186- ?_296+?del E13/E2 1 p.N1303K/p.N1303K E21/E21 2 p.N1303K/p.S945L E21/E15 1 p.N1303K/c.1677delTA E21/E10 1 p.G542X/p.G542X E11/E11 2 p.G542X/c.2789+5GNA E11/I14b 1 c.3120+1GNA/c.3120+1GNA I16/I16 2 c.3120+1GNA/c.3121-1GNA I16 1 c.3121-1GNA/p.T1086I I16/E17b 1 c.3130delA/c.3130delA E17a/E17a 2 p.D192G/p.D192G E5/E5 1 p.R334W/p.R334W E7/E7 1 p.R334W/p.S945L E7/E15 1 p.R334W/p.L1077P E7/E17b 1 c.1525-1GNA/c.1525-1GNA I9/I9 1 p.S549R/p.S549R E11/E11 1 p.A566D/p.A566D E12/E12 1 c.1898+1GNT/c.1898+1GNT I12/I12 1 c.2576delA/p.S1455X/ E13/E24 1 c.2184insA/c.1677delTA E10/E13 1 p.R785X/p.R785X E13/E13 1 c.2752-1_2756delGGTGGCinsTTG/ c.2752-1_2756delGGTGGCinsTTG I14a/E14b 1 c.2789+5GNA/c.2789+5GNA I14b/I14b 1 p.K1177X/p.K1177X E19/E19 1 c.406-?_1716+?del/c.406-?_1716+?del E4-E10/E4-E10 1 Total 53 origin were extensively studied for the presence of mutations in the CFTR gene, for the presence of the deep intronic 3849+10 kbC→T mutation, and large deletions/ duplications. Login to comment 67 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Screening of the samples for ten mutations with an ARMS-PCR assay only revealed the identification of three mutations: p.F508del was found in 25 (18.1%) alleles, p.N1303K in six (4.3%) alleles, and p.G542X in five (3.6%) alleles (Table 1), the remainder mutations in the CFTR coding region, and its exon/intron junctions, were found by sequencing and the MLPA assay, which are given in Table 1. Login to comment 89 ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser466* Eight other mutations were found with a frequency greater than 2%: c.2183_2184delAAinsG (6.5%), p.S466X (5.8%), p.N1303K (4.3%), c.2789+5GNA (4.3%), p.G542X (3.6%), c.3120+ 1GNA (3.6%), p.R334W (2.9%), and c.3130delA (2.9%). Login to comment 90 ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser466* Eight other mutations were found with a frequency greater than 2%: c.2183_2184delAAinsG (6.5%), p.S466X (5.8%), p.N1303K (4.3%), c.2789+5GNA (4.3%), p.G542X (3.6%), c.3120+ 1GNA (3.6%), p.R334W (2.9%), and c.3130delA (2.9%). Login to comment 92 ABCC7 p.Ile148Thr In the five patients with a broad spectrum of respiratory diseases or undefined pancreatic disease and borderline (40-60 mmol/l) sweat chloride values, the heterozygous state for 1 mutation was found, i.e. the c.3499+37GNA, c.2789+5GNA, c.406-8TNC, c.3850-24GNA, and the p.I148T polymorphism. Login to comment 93 ABCC7 p.Ile148Thr In the five patients with a broad spectrum of respiratory diseases or undefined pancreatic disease and borderline (40-60 mmol/l) sweat chloride values, the heterozygous state for 1 mutation was found, i.e. the c.3499+37GNA, c.2789+5GNA, c.406-8TNC, c.3850-24GNA, and the p.I148T polymorphism. Login to comment 95 ABCC7 p.Ser1455* It was found once in a patient that carried S1455X in compound heterozygosity. Login to comment 96 ABCC7 p.Ser1455* It was found once in a patient that carried S1455X in compound heterozygosity. Login to comment 98 ABCC7 p.Ala566Asp The p.A566D mutation is located in exon 12 and was found in homozygous state in 1 consanguineous patient who has a classical CF phenotype. Login to comment 99 ABCC7 p.Ala566Asp The p.A566D mutation is located in exon 12 and was found in homozygous state in 1 consanguineous patient who has a classical CF phenotype. Login to comment 105 ABCC7 p.Thr1036Ile The p.T1036I missense mutation is located in exon 17a, and was found in one patient who carried p.F508del in compound heterozygosity. Login to comment 106 ABCC7 p.Thr1036Ile The p.T1036I missense mutation is located in exon 17a, and was found in one patient who carried p.F508del in compound heterozygosity. Login to comment 115 ABCC7 p.Trp1145Arg The CBAVD patient, without pulmonary disease, was homozygous for the p.W1145R mutation. Login to comment 116 ABCC7 p.Trp1145Arg The CBAVD patient, without pulmonary disease, was homozygous for the p.W1145R mutation. Login to comment 130 ABCC7 p.Ser466* The third most prevalent mutation in Iran was p.S466X. Login to comment 131 ABCC7 p.Ser466* The third most prevalent mutation in Iran was p.S466X. Login to comment 135 ABCC7 p.Asn1303Lys The fourth (and fifth) most common mutations in Iran were p.N1303K (4.3%) and c.2789+5GNA (4.3%). Login to comment 136 ABCC7 p.Asn1303Lys The fourth (and fifth) most common mutations in Iran were p.N1303K (4.3%) and c.2789+5GNA (4.3%). Login to comment 138 ABCC7 p.Asn1303Lys The p.N1303K mutation is found worldwide at a rather high frequency (1.3%). Login to comment 139 ABCC7 p.Asn1303Lys The p.N1303K mutation is found worldwide at a rather high frequency (1.3%). Login to comment 141 ABCC7 p.Gly542* The p.G542X mutation accounts for 2.4% of the CFTR mutations worldwide [13,21]. Login to comment 142 ABCC7 p.Gly542* The p.G542X mutation accounts for 2.4% of the CFTR mutations worldwide [13,21]. Login to comment 143 ABCC7 p.Gly542* Two patients carried p.G542X in homozygous state, of which one was consanguineous, and one was compound heterozygous with c.2789+5GNA. Login to comment 144 ABCC7 p.Gly542* Two patients carried p.G542X in homozygous state, of which one was consanguineous, and one was compound heterozygous with c.2789+5GNA. Login to comment 154 ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Lys68Glu ABCC7 p.Arg170His ABCC7 p.Ser466* Possible explanations for failure to detect all mutations are: the mutations that are in intron sequences far from coding Table 3 CFTR mutation panel recommended for screening in Iranian CF patients Mutation Number of chromosomes Frequency p.F508del 25 18.1% c.2183_2184delAAinsG 9 6.5% p.S466X 8 5.8% p.N1303K 6 4.3% c.2789+5GNA 6 4.3% p.G542X 5 3.6% c.3120+1GNA 5 3.6% p.R334W 4 2.9% c.3130delA 4 2.9% Total 72 52.0% Table 4 Clinical features and some polymorphisms in 7 Iranian patients; in these patients a mutation could only be found on one CFTR gene Genotype PI/PS Sweat (Cl- ) TGm Tn (In8) GATT (In6a) 1001+11 (In6b) M470V p.K68E/UÌe; PI 80 TG10-T7_TG10-T7 GATT 7/7 C A c.406-8TNC/U PI 50 TG12-T7_TG11-T7 GATT 6/7 C A/G c.406-3TNC/U PI 90 TG11-T7_TG11-T7 GATT 7/7 C G p.R170H/U PS 80 TG11-T7_TG10-T7 GATT 7/7 C A/G c.3850-24GNA/U PI 55 TG11-T7_TG11-T7 GATT 7/7 C G c.2789+5GNA/U PI 50 TG11-T7_TG10-T7 GATT 7/7 C A/G c.2043delG/U PS 70 TG12-T7_TG10-T7 GATT 6/7 C A Ìe;Unknown mutations; PS, indicates pancreatic sufficient; PI, pancreatic sufficient. Login to comment 155 ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Lys68Glu ABCC7 p.Arg170His ABCC7 p.Ser466* Possible explanations for failure to detect all mutations are: the mutations that are in intron sequences far from coding Table 3 CFTR mutation panel recommended for screening in Iranian CF patients Mutation Number of chromosomes Frequency p.F508del 25 18.1% c.2183_2184delAAinsG 9 6.5% p.S466X 8 5.8% p.N1303K 6 4.3% c.2789+5GNA 6 4.3% p.G542X 5 3.6% c.3120+1GNA 5 3.6% p.R334W 4 2.9% c.3130delA 4 2.9% Total 72 52.0% Table 4 Clinical features and some polymorphisms in 7 Iranian patients; in these patients a mutation could only be found on one CFTR gene Genotype PI/PS Sweat (Cl- ) TGm Tn (In8) GATT (In6a) 1001+11 (In6b) M470V p.K68E/U⁎ PI 80 TG10-T7_TG10-T7 GATT 7/7 C A c.406-8TNC/U PI 50 TG12-T7_TG11-T7 GATT 6/7 C A/G c.406-3TNC/U PI 90 TG11-T7_TG11-T7 GATT 7/7 C G p.R170H/U PS 80 TG11-T7_TG10-T7 GATT 7/7 C A/G c.3850-24GNA/U PI 55 TG11-T7_TG11-T7 GATT 7/7 C G c.2789+5GNA/U PI 50 TG11-T7_TG10-T7 GATT 7/7 C A/G c.2043delG/U PS 70 TG12-T7_TG10-T7 GATT 6/7 C A ⁎Unknown mutations; PS, indicates pancreatic sufficient; PI, pancreatic sufficient. 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