ABCMdb

PMID: 15698945

Dugueperoux I, De Braekeleer M
Genotype-phenotype relationship for five CFTR mutations frequently identified in western France.
J Cyst Fibros. 2004 Dec;3(4):259-63., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC7 p.Trp846* ABCC7 p.Glu60* Then we extracted the available data for all the compound heterozygotes carrying the DF508 allele and one of the following mutations: DI507, 1078delT, 4005+1G-NA, E60X and W846X, and matched a patient homozygous for the DF508 mutation for each of them. Login to comment 6 ABCC7 p.Trp846* Results: Western France appeared to have a specific distribution of some CF mutations. Furthermore, disparities were found regarding the mutation repartition (DI507 in Normandy, 1078delT, 4005+1G-NA and W846X in western Brittany). Login to comment 9 ABCC7 p.Trp846* ABCC7 p.Glu60* Although the W846X and E60X mutations should be considered as severe alleles as regards to pancreatic function, they were associated with less severe pulmonary manifestations and, probably, better prognosis. Login to comment 12 ABCC7 p.Trp846* ABCC7 p.Glu60* Keywords: Cystic fibrosis; DI507; 4005+1G-NA; 1078delT; E60X; W846X; Genotype-phenotype; Rare mutations; France 1. Login to comment 33 ABCC7 p.Trp846* ABCC7 p.Glu60* In a second step, we extracted the available data for all the compound heterozygotes carrying the DF508 allele and one of the following mutations: DI507, 1078delT, 4005+1G-NA, E60X and W846X, as previously described [15]. Login to comment 34 ABCC7 p.Trp846* ABCC7 p.Glu60* In a second step, we extracted the available data for all the compound heterozygotes carrying the DF508 allele and one of the following mutations: DI507, 1078delT, 4005+1G-NA, E60X and W846X, as previously described [15]. Login to comment 43 ABCC7 p.Trp846* ABCC7 p.Glu60* Five CFTR mutations (DI507, 4005+1G-NA, 1078delT, E60X and W846X) were more commonly identified in western France than in the other regions ( pb0.05 for all but one alleles). Login to comment 44 ABCC7 p.Trp846* ABCC7 p.Glu60* Five CFTR mutations (DI507, 4005+1G-NA, 1078delT, E60X and W846X) were more commonly identified in western France than in the other regions ( pb0.05 for all but one alleles). Login to comment 66 ABCC7 p.Trp846* ABCC7 p.Glu60* ABCC7 p.Glu60* Table 1 Distribution of the CF alleles in western France and in the other French regions Western France Other regions Number of alleles Frequency (%) Number of alleles Frequency (%) DI507 16 0.97 36 0.55 1078delT 33 2.00 12 0.18 4005+1G-NA 6 0.36 13 0.20 E60X 7 0.43 3 0.05 W846X 9 0.55 7 0.11 DF508 1118 68.00 4031 61.22 Other mutations 306 18.61 1376 20.90 Unknown mutations 149 9.06 1106 16.80 Total 1644 6584 I. Dugue´pe´roux, M. De Braekeleer / Journal of Cystic Fibrosis 3 (2004) 259-263260 Nine pairs of E60X/DF508 and DF508 /DF508 patients were included in the present study (Table 3). Login to comment 67 ABCC7 p.Trp846* ABCC7 p.Glu60* ABCC7 p.Glu60* Table 1 Distribution of the CF alleles in western France and in the other French regions Western France Other regions Number of alleles Frequency (%) Number of alleles Frequency (%) DI507 16 0.97 36 0.55 1078delT 33 2.00 12 0.18 4005+1G-NA 6 0.36 13 0.20 E60X 7 0.43 3 0.05 W846X 9 0.55 7 0.11 DF508 1118 68.00 4031 61.22 Other mutations 306 18.61 1376 20.90 Unknown mutations 149 9.06 1106 16.80 Total 1644 6584 Nine pairs of E60X/DF508 and DF508 /DF508 patients were included in the present study (Table 3). Login to comment 68 ABCC7 p.Glu60* The mean height and weight Z scores were higher among the E60X/DF508 patients but not statistically different from those of DF508 homozygous patients. Login to comment 69 ABCC7 p.Glu60* The mean height and weight Z scores were higher among the E60X/DF508 patients but not statistically different from those of DF508 homozygous patients. Login to comment 70 ABCC7 p.Glu60* The mean FEV1 and FCV values were much higher among the E60X/DF508 patients but not significantly different from those of the DF508 homozygotes. Login to comment 71 ABCC7 p.Glu60* ABCC7 p.Glu60* Seven out of the nine E60X/DF508 patients had pancreatic insufficiency. Login to comment 72 ABCC7 p.Trp846* ABCC7 p.Glu60* Ten W846X/DF508 patients were included in the study (Table 3). Login to comment 73 ABCC7 p.Trp846* ABCC7 p.Trp846* ABCC7 p.Trp846* ABCC7 p.Glu60* ABCC7 p.Glu60* All of them had a G to A change at nucleotide Table 2 Distribution of the five CFTR alleles in the three regions of western France DI507 1078delT 4005+1G-NA E60X W846X Brittany 6(37.5%) 28(84.8%) 6(100.0%) 5(71.3%) 5(55.5%) Normandy 8(50.0%) 2(6.1%) 0 2(28.7%) 3(33.3%) Pays-de-Loire 2(12.5%) 3(9.1%) 0 0 1(11.2%) Western France 16(100.0%) 33(100.0%) 6(100.0%) 7(100.0%) 9(100.0%) Table 3 Clinical and laboratory findings of the CF patients distributed in the five genotype groups DI507/DF508 4005+1G-NA/DF508 1078delT/DF508 E60X/DF508 W846X/DF508 Sex (males/females) 10/11 4/6 13/10 2/7 4/6 Age on Jan 1, 2001 (years)* Mean age onFS.D. Login to comment 74 ABCC7 p.Trp846* ABCC7 p.Trp846* ABCC7 p.Glu60* ABCC7 p.Glu60* All of them had a G to A change at nucleotide Table 2 Distribution of the five CFTR alleles in the three regions of western France DI507 1078delT 4005+1G-NA E60X W846X Brittany 6(37.5%) 28(84.8%) 6(100.0%) 5(71.3%) 5(55.5%) Normandy 8(50.0%) 2(6.1%) 0 2(28.7%) 3(33.3%) Pays-de-Loire 2(12.5%) 3(9.1%) 0 0 1(11.2%) Western France 16(100.0%) 33(100.0%) 6(100.0%) 7(100.0%) 9(100.0%) Table 3 Clinical and laboratory findings of the CF patients distributed in the five genotype groups DI507/DF508 4005+1G-NA/DF508 1078delT/DF508 E60X/DF508 W846X/DF508 Sex (males/females) 10/11 4/6 13/10 2/7 4/6 Age on Jan 1, 2001 (years)* Mean age onFS.D. Login to comment 85 ABCC7 p.Trp846* More DF508 homozygotes than W846X/DF508 patients were colonized with Pseudomonas aeruginosa, the difference being borderline significant ( p=0.057). Login to comment 86 ABCC7 p.Trp846* ABCC7 p.Trp846* The mean FEV1 and FCV values were much higher among the W846X/DF508 patients but not significantly. Login to comment 87 ABCC7 p.Trp846* The mean FEV1 and FCV values were much higher among the W846X/DF508 patients but not significantly. Login to comment 89 ABCC7 p.Trp846* ABCC7 p.Glu60* One was W846X/ DF508, another DI507/DF508 and the last one E60X/DF508. Login to comment 90 ABCC7 p.Trp846* ABCC7 p.Glu60* One was W846X/ DF508, another DI507/DF508 and the last one E60X/DF508. Login to comment 92 ABCC7 p.Glu60* The E60X allele is also mentioned but as an uncommon CF mutation in specific populations. Login to comment 93 ABCC7 p.Glu60* ABCC7 p.Glu60* Indeed, in Belgium, the frequency of the E60X allele ranges from 1.0% to 2.1% [18]. Login to comment 94 ABCC7 p.Trp846* ABCC7 p.Glu60* No data are found on the 4005+1G-NA and W846X alleles in the CF database. Login to comment 95 ABCC7 p.Trp846* No data are found on the 4005+1G-NA and W846X alleles in the CF database. Login to comment 100 ABCC7 p.Trp846* ABCC7 p.Glu60* Scotet et al. [4] reported a frequency over 3.5% for the 1078delT mutation, 0.8% for the 4005+1G-NA, 1.1% for the W846X and 0.7% for the E60X. Login to comment 101 ABCC7 p.Trp846* ABCC7 p.Trp846* ABCC7 p.Glu60* A founder effect was also postulated for the 1078delT and W846X mutations [16]. Login to comment 102 ABCC7 p.Trp846* A founder effect was also postulated for the 1078delT and W846X mutations [16]. Login to comment 106 ABCC7 p.Glu60* Although not statistically different, the age at diagnosis and the Z scores of height and weight were higher in the E60X/DF508 group than among the DF508 homozygotes. Login to comment 107 ABCC7 p.Glu60* Although not statistically different, the age at diagnosis and the Z scores of height and weight were higher in the E60X/DF508 group than among the DF508 homozygotes. Login to comment 108 ABCC7 p.Glu60* The age distribution of the CF patients compound heterozygous for the E60X is also different from that of the DF508 homozygotes present in the French CF Registry, 67% being 15 years old and over compared to 40%. Login to comment 109 ABCC7 p.Trp846* ABCC7 p.Glu60* Statistically, no distinction can be made between the W846X/DF508 compound heterozygotes and the DF508 homozygotes except for a higher risk of diarrhoea at the time of diagnosis ( p=0.02). Login to comment 110 ABCC7 p.Trp846* Statistically, no distinction can be made between the W846X/DF508 compound heterozygotes and the DF508 homozygotes except for a higher risk of diarrhoea at the time of diagnosis ( p=0.02). Login to comment 112 ABCC7 p.Trp846* ABCC7 p.Glu60* In the present study, patients carrying a stop mutation, either E60X or W846X, associated with DF508 have higher age at diagnosis, higher anthropometric and pulmonary function parameters, the mean BMI values being within the normal brackets. Login to comment 113 ABCC7 p.Trp846* ABCC7 p.Glu60* In the present study, patients carrying a stop mutation, either E60X or W846X, associated with DF508 have higher age at diagnosis, higher anthropometric and pulmonary function parameters, the mean BMI values being within the normal brackets. Login to comment 126 ABCC7 p.Trp846* In conclusion, western France appears to have a specific distribution of some CF mutations. Furthermore, disparities are found regarding the mutation repartition (DI507 in Normandy, 1078delT, 4005+1G-NA and W846X in western Brittany). Login to comment 127 ABCC7 p.Trp846* In conclusion, western France appears to have a specific distribution of some CF mutations. Furthermore, disparities are found regarding the mutation repartition (DI507 in Normandy, 1078delT, 4005+1G-NA and W846X in western Brittany). Login to comment 130 ABCC7 p.Trp846* ABCC7 p.Glu60* CF patients carrying the E60X or W846X allele have better anthropometric and lung functional results combined with a higher probability of reaching adulthood. Login to comment 131 ABCC7 p.Trp846* ABCC7 p.Trp846* ABCC7 p.Glu60* ABCC7 p.Glu60* This leads us to conclude that, although the W846X or E60X mutations should be considered as severe alleles as regards to pancreatic function, they are associated with less severe pulmonary manifestations and, probably, better prognosis. Login to comment 132 ABCC7 p.Trp846* ABCC7 p.Glu60* This leads us to conclude that, although the W846X or E60X mutations should be considered as severe alleles as regards to pancreatic function, they are associated with less severe pulmonary manifestations and, probably, better prognosis. Login to comment