ABCMdb

PMID: 11354633

Tzetis M, Efthymiadou A, Strofalis S, Psychou P, Dimakou A, Pouliou E, Doudounakis S, Kanavakis E
CFTR gene mutations--including three novel nucleotide substitutions--and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease.
Hum Genet. 2001 Mar;108(3):216-21., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCC7 p.Val11Ile Three potentially disease-causing mutations, T388 M, M1R and V11I, are novel, found so far only in three asthma patients. Login to comment 44 ABCC7 p.Val11Ile A total of 17 different mutations deemed to be involved in disease predisposition, including three novel mutations (T388 M, M1R, V11I), were identified in 16 patients. Login to comment 45 ABCC7 p.Ser977Phe More specifically, CFTR mutations were found in 9/20 patients with asthma (P<0.05), in 5/19 patients with DB (P>0.05) - one of whom was a compound heterozygote (F508del/S977F) - and in 2/12 patients with COPD (P>0.05). Login to comment 47 ABCC7 p.Ile148Thr ABCC7 p.Ser1235Arg ABCC7 p.Ala120Thr ABCC7 p.Arg297Gln ABCC7 p.Leu997Phe ABCC7 p.Tyr301Cys ABCC7 p.Ser977Phe ABCC7 p.Thr896Ile Of the 17 mutations in the patients, 9 (Y301C, I148T, R297Q, S1235R, T896I, S977F, L997F, F1052 V, A120T) have been listed by the Cystic Fibrosis Genetic Analysis Consortium (see website: http://www.cf.genet.sickkids. Login to comment 48 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys ABCC7 p.Ile1027Thr on.ca) as disease-causing mutations, while 3 (R668C, R75Q, I1027T) have been listed as sequence polymorphisms. Login to comment 49 ABCC7 p.Arg75Gln ABCC7 p.Arg668Cys R75Q and R668C have been reported with high frequencies in patients with DB, asthma and congenital bilateral absence of vas deferens (CBAVD) (Pignatti et al. 1995; Pignatti et al. 1996; Girodon et al. 1997; Lazaro et al. 1999; Kanavakis et al. 1998). Login to comment 50 ABCC7 p.Asp565Gly Mutation D565G had previously been reported in a CBAVD patient (Kanavakis et al. 1998). Login to comment 51 ABCC7 p.Val11Ile Three novel mutations, T388 M, M1R and V11I, were first identified in this study, and were found only among asthma patients, not in the control group or in the other pulmonary disease patients. Login to comment 55 ABCC7 p.Val11Ile 217 Novel mutations In this study three novel missense mutations in highly conserved residues (Tucker et al. 1992), T388 M, M1R and V11I, were found in the asthma patients. Login to comment 60 ABCC7 p.Ile148Thr ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Ala120Thr ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln ABCC7 p.Arg297Gln ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Ile1027Thr ABCC7 p.Tyr301Cys ABCC7 p.Ser977Phe ABCC7 p.Thr896Ile ABCC7 p.Asp565Gly ABCC7 p.Asp565Gly ABCC7 p.Asp565Gly 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 61 ABCC7 p.Val11Ile The V11I (G to A at nucleotide 163 of exon 1) is a conservative amino acid substitution. Login to comment 72 ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Ala120Thr ABCC7 p.Arg668Cys ABCC7 p.Arg297Gln ABCC7 p.Leu997Phe ABCC7 p.Ile1027Thr ABCC7 p.Tyr301Cys ABCC7 p.Ser977Phe ABCC7 p.Thr896Ile ABCC7 p.Asp565Gly The proportion of CFTR alleles in each group is expressed as c/d (e), where c indicates the number of alleles with the genotype indicated at left, d indicates the number of total alleles examined in each group and e represents the percentage aMutation name according to the Cystic Fibrosis Genetic Analysis Consortium bNovel mutations, reported for the first time in this study Mutationa Control Pulmonary disease patients Greek CF population patients (PS; PI) (n=52) Asthma DB COPD (n=426) (n=20) (n=19) (n=12) R75Q (356 G/A, exon 3) 1 (0.96%) 1 (2.5%) - - 1 (0.1%) R668C (2134 C/T, exon 13) 2 (1.9%) - 1 (2.6%) - 1 (0.1%) L997F (3123 G>C, exon 17a) 1 (0.96%) 2 (5%) - - - F508del 1 (0.96%) - 2 (5.3%) - 465 (54.6%) D565G (A>G at 1825, exon 12) 2 (1.9%) - 1 (2.6%) - 1 (0.1%) F1052 V (T>G at 3286, exon 17b) 2 (1.9%) - - 1 (4.2%) 1 (0.1%) R297Q (G>A at 1022, exon 7) 1 (0.96%) 2 (5%) - - - Y301C (A>G at 1034, exon 7) - 1 (2.5%) - - - I148T (T>C at 575, exon 4) - 2 (5%) - - 1 (0.1%) T388Mb (C>T at 1295, exon 8) - 1 (2.5%) - - - M1Rb (T>G at 134, exon 1) - 1 (2.5%) - - - V11Ib (G>A at 163, exon 1) - 1 (2.5%) - - - I1027T (3212 T/C, exon 17a) - - 1 (2.6%) - 1 (0.1%) T896I (C>T at 2819, exon 15) - - 1 (2.6%) - - S977F (C>T at 3062, exon 16) - - 1 (2.6%) - - A120T (G>A at 490, exon 4) - 1 (2.5%) - - - S1235R (T>G at 3837, exon 19) - - - 1 (4.2%) - Table 3 Frequency of M470 and (TG)mTn alleles in pulmonary disease patients and controls (DB disseminated bronchiectasis, COPD chronic obstructive pulmonary disease, n number of cases, ND not detected) Clinical status Allele M470 TG11/T7 TG10/T7 TG12/T7 TG10/T9 TG11/T5 TG12/T5 TG13/T5 Asthmaa (n=20) 13 (32.5%) 23 (57.5%) 3 (7.5%) 5 (12.5%) 3 (7.5%) 2 (5%) ND 1 (2.5%) DB (n=19) 17 (44.7) 18 (47.4%) 6 (15.8%) 4 (10.5%) 9 (23.7%) ND 1 (2.6%) ND COPD (n=12) 17 (70.8) 12 (50%) 5 (20.8%) 1 (4.2%) 4 (16.7%) 1 (4.2%) 1 (4.2%) ND Controls (n=52) 37 (35.5%) 71 (68.%) 23 (22.1%) 1 (0.96%) 6 (5.8%) 1 (0.96%) ND ND aAlleles TG11/T9 (2) and TG9/T9 (1) also detected alleles, P<0.01) were both found more frequently in patients with COPD. Login to comment 75 ABCC7 p.Ala120Thr ABCC7 p.Arg297Gln Of them, one was homozygous for the IVS8-5T allele and also carried mutation R297Q, and another carrier of mutation A120T was heterozygous for the IVS8-5T allele. Login to comment 76 ABCC7 p.Ala120Thr ABCC7 p.Arg297Gln The phase of the IVS8-5T allele regarding the A120T mutation is not known, but the patient with the R297Q mutation could be considered a CF compound heterozygote. Login to comment 77 ABCC7 p.Leu997Phe Mutation L997F, previously reported with high frequency in asthma patients, was found twice in this study. Login to comment 81 ABCC7 p.Arg668Cys ABCC7 p.Ile1027Thr ABCC7 p.Asp565Gly Two patients had two mutations each (F508del and I1027T; D565G and R668C). Login to comment 83 ABCC7 p.Asp565Gly Mutation D565G is a novel Greek mutation previously reported by us in a CBAVD patient (Kanavakis et al. 1998). Login to comment 84 ABCC7 p.Arg668Cys It is interesting that this CBAVD patient also carried R668C, had a negative sweat chloride test, but no pulmonary symptoms. Login to comment 90 ABCC7 p.Thr896Ile Mutation T896I, previously reported in an asthma patient, was found in one DB patient. Login to comment 93 ABCC7 p.Ile148Thr Mutation I148T is a CF-causing mutation, first reported in a pancreatic-insufficient CF patient (Cystic Fibrosis Genetic Analysis Consortium website). Login to comment 94 ABCC7 p.Ser977Phe One DB patient was a compound heterozygote, F508del/ S977F, and also carried the IVS8-5T allele. Login to comment 96 ABCC7 p.Ser1235Arg COPD patients Amongst the 12 COPD patients, two carried mutations F1052 V and S1235R. Login to comment 102 ABCC7 p.Ala120Thr ABCC7 p.Arg297Gln Two asthma patients (genotypes: R297Q/-, A120T/-) carried haplotypes TG13/T5/M470, TG11/T5/M470 and TG11/T5/V470, which have been found almost exclusively among CBAVD patients and not among those with normal CFTR genes (Costes et al. 1995). Login to comment 105 ABCC7 p.Arg297Gln In the case of the asthma patient, the milder mutation R297Q could, in association with the particular haplotype, produce the phenotype of asthma. Login to comment