ABCMdb

PMID: 8933333

Vazquez C, Antinolo G, Casals T, Dapena J, Elorz J, Seculi JL, Sirvent J, Cabanas R, Soler C, Estivill X
Thirteen cystic fibrosis patients, 12 compound heterozygous and one homozygous for the missense mutation G85E: a pancreatic sufficiency/insufficiency mutation with variable clinical presentation.
J Med Genet. 1996 Oct;33(10):820-2., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Gly85Glu Received 4 December 1995 Revised version accepted for publication 28 May 1996 Abstract To study the severity of mutation G85E, located in the first membrane spanning domain of the CFTR gene, we studied the clinical features of 13 Spanish patients with cystic fibrosis (CF) carrying this mutation. Login to comment 2 ABCC7 p.Gly85Glu G85E accounts for about 1% of Spanish CF alleles. Login to comment 3 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu One patient was homozygous G85E/G85E and the rest were compound heterozygotes for G85E and other mutations (AF508 nine patients, A1507 two patients, and 712-1G>T one patient). Login to comment 4 ABCC7 p.Gly85Glu The characteristics ofthe pooled G85E/any mutation group were compared with those of30 AF508 homozygotes. Login to comment 5 ABCC7 p.Gly85Glu Mean age at diagnosis and percentage of ideal height for age were higher in the G85E/any mutation group (4.2 (SD 4.7) v 2.4 (SD 2.3), p<0.05, and 102.8 (SD 4.7) v 97.8 (SD 4.1), p<0.01)), both probably related to the greater prevalence of pancreatic sufficiency (70% v 0%, p<0O01). Login to comment 6 ABCC7 p.Gly85Glu The G85E homozygote was pancreatic sufficient. Login to comment 7 ABCC7 p.Gly85Glu Sweat sodium levels were slighdy higher, and salt loss related problems more frequent, in the G85E/any group. Login to comment 8 ABCC7 p.Gly85Glu Two of the G85E patients died ofrespiratory failure aged 6 and 14 years. Login to comment 10 ABCC7 p.Gly85Glu (JMed Genet 1996;33:820-822) Key words: cystic fibrosis; CFTR mutations; phenotype; G85E mutation. Login to comment 17 ABCC7 p.Gly85Glu '8 Other mutations associated with mild CF are some splicing mutations in which low levels of normal transcripts are produced.6 17 We present here the clinical findings in 13 Spanish CF patients carrying the missense mutation G85E, a G to A change at nucleotide position 386 in exon 3, which results in a glutamic acid for glycine substitution at codon 85 in the first MSD of the CFTR. Login to comment 21 ABCC7 p.Gly85Glu The clinical features of patients with a G85E/any mutation genotype were compared with those of 30 AF508 homozygotes under control at Hospital de Cruces. Login to comment 26 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu The best FEV1 over the last year was chosen as an index of pulmonary group.bmj.comon October 25, 2012 - Published byjmg.bmj.comDownloaded from Thirteen cystic fibrosis patients compound heterozygous or homozygous for G85E mutation Table 1 Clinicalfeatures of 13 CFpatients carrying the G85E mutation compared with AF508 homozygotes Genotype Parameter G85Elany AF5081AF508 No of patients 13 30 Sex: female/male 6/7 12/18 Alive 11 28 Mean, SD (No studied) Current age (y) 8.4, 5.4 (11) 9.9, 4.3 (28) Age at diagnosis (y) 4.23,4.7 (13) 2.4, 2.3 (30)* Sweat sodium (mmol/l) 105.1, 17.0 (7) 94.3, 14.0 (23)* Sweat chloride (mmol/l) 107.2, 4.0 (5) 97.5, 14.0 (22) Schwachman score 87.5, 7.5 (10) 88.7, 9.4 (28) Chrispin-Norman chest x ray score 4.5, 3.1 (9) 4.7, 5.3 (27) FEVI (% predicted) 80.2, 8.2 (6) 87.1, 13 (24) FVC (% predicted) 85.3, 7.7 (6) 94.8, 14.6 (24) % Ideal body weight 101.4, 14.2 (10) 100.7, 11.2 (28) % Ideal body height 102.8, 4.7 (10) 97.8, 4.1 (28)** No positivelNo studied (%) Pancreatic insufficiency 4/13 (30.7) 30/30 (100)** Colonisation with P aeruginosa 10/13 (76.9) 24/30 (80) Chronic bronchial infection with P aeruginosa 5/13 (38.4) 10/30 (33.3) Meconium ileus 0/13 (0) 2/30 (6.7) Liver disease 1/13 (7.6) 2/30 (6.7) Dehydration and metabloic alkalosis 4/13 (30.7) 1/30 (3.4)* *p<0.05, **p<0.01. Login to comment 32 ABCC7 p.Gly85Glu Direct sequencing allowed us to identify the G85E mutation. Login to comment 34 ABCC7 p.Gly85Glu G85E was found in 13 samples. Login to comment 35 ABCC7 p.Gly85Glu All chromosomes with mutation G85E were associated with the same microsatellite haplotype 16-24-13. Login to comment 36 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu Nine patients were compound heterozygotes for AF508/G85E, one pair of sibs were G85E/AI507, one was G85E/712-1 G>T, and one was a G85E homozygote. Login to comment 37 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu Data from G85E/AF508 and G85E/non-AF508 patients were pooled for comparison with those from AF508 homozygotes. Login to comment 38 ABCC7 p.Gly85Glu The G85E/any mutation patients were older at diagnosis, had a higher percentage of ideal height, and a lower prevalence of PI (30% v 100%, p<0.01) compared with the AF508 homozygotes (table 1). Login to comment 42 ABCC7 p.Gly85Glu Ages at death were 6 and 14 years in the G85E/any group, and 16 and 18 years in the AF508 homozygous group. Login to comment 44 ABCC7 p.Gly85Glu The G85E homozygote was a 17 year old girl with pancreatic sufficiency (PS), who had recurrent coughing from the age of 4 and was diagnosed at the age of 13 years. Login to comment 51 ABCC7 p.Gly85Glu The worldwide prevalence of G85E is 0.2%,4 but higher frequencies have been reported in the US (0.7%),24 Italy (1.7%),25 and Spain (1%) (T Casals, personal communication). Login to comment 53 ABCC7 p.Gly85Glu The molecular mechanism of the CFTR dysfunction associated with G85E has recently been found to consist of a trafficking defect (class II mutation)6 with rapid degradation of the mutant protein before transit through the Golgi complex.26 There have been only three reports on the clinical characteristics associated with this mutation. Login to comment 54 ABCC7 p.Gly85Glu Chalkley and Harris27 described an 11 year old boy, homozygous for G85E, with PS. Login to comment 55 ABCC7 p.Gly85Glu Kerem et af8 reported five G85E homozygotes and eight compound Table 2 Characteristics of 13 CFpatients with mutation G85E* Patient Agelage at Pancreatic FEVI (% No Sex diagnosis (y) status Schwachman CBI pred) Other clinicalfeatures 1 F 17.6/13.3 PS 95 No 75 Mild pulmonary disease 2 F 14 (dead)/0.7 PSt - Yes 28 Dehydration. Login to comment 62 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu Older sib of patient 8 * Patient 1 was G85E/G85E, patients 8 and 13 G85E/AI507, patient 9 G85E/712-1G>T, and the rest G85E/AF508. Login to comment 65 ABCC7 p.Gly85Glu Friedman et af4 reported that six out of their nine patients with G85E had PS. Login to comment 66 ABCC7 p.Gly85Glu The data presented here suggest that G85E is predominantly associated with PS. Login to comment 67 ABCC7 p.Gly85Glu This inconsistent association of G85E with PS, and the clinical discordance in our two pairs of sibs, suggest that genetic factors other than CF genotype, as well as environmental factors, are involved in the severity of the disease. Login to comment 68 ABCC7 p.Gly85Glu These factors seem more evident when the CF mutations are mild, as has been shown for mutation R334W7 or for the IVS8-6(5T) mutation, which is associated with male infertility, mild CF, or even a normal phenotype.8 In summary G85E occurred with PS in 70% of the cases. Login to comment 69 ABCC7 p.Gly85Glu Compared with AF508 homozygotes, patients with G85E were diagnosed later, were taller, and had a higher prevalence of dehydration, but no other difference was observed either in the severity of the pulmonary disease or in the prevalence of other CF related complications.This mutation also shows intrafamilial variability in its clinical presentation. Login to comment 70 ABCC7 p.Gly85Glu Further experience over a longer time span is needed to clarify the comparative severity of the phenotype associated with G85E. Login to comment 89 ABCC7 p.Arg334Trp 7 Estivill X, Ortigosa I, Perez Frias J, et al. Clinical characteristics of 16 cystic fibrosis patients with the missense mutation R334W, a pancreatic insufficiency mutation with variable age of onset and interfamilial clinical differences. Login to comment 90 ABCC7 p.Arg334Trp 7 Estivill X, Ortigosa I, Perez Frias J, et al. Clinical characteristics of 16 cystic fibrosis patients with the missense mutation R334W, a pancreatic insufficiency mutation with variable age of onset and interfamilial clinical differences. Login to comment 95 ABCC7 p.Leu206Trp 10 Rozen R, Ferreira-Rajabi L, Robb L, Colman N. L206W mutation of the cystic fibrosis gene, relatively frequent in French Canadians, is associated with atypical presentations of cystic fibrosis. Login to comment 97 ABCC7 p.Leu206Trp 10 Rozen R, Ferreira-Rajabi L,Robb L, Colman N. L206W mutation of the cystic fibrosis gene, relatively frequent in French Canadians, is associated with atypical presentations of cystic fibrosis. Login to comment 100 ABCC7 p.Glu92Lys A new missense mutation (E92K) in the first transmembrane domain of the CFTR gene causes a benign cystic fibrosis phenotype. Login to comment 102 ABCC7 p.Glu92Lys A new missense mutation (E92K) in the first transmembrane domain of the CFTR gene causes a benign cystic fibrosis phenotype. Login to comment 103 ABCC7 p.Pro205Ser Identification of a new missense mutation (P205S) in the first transmembrane domain of the CFTR gene associated with a mild cystic fibrosis phenotype. Login to comment 105 ABCC7 p.Pro205Ser Identification of a new missense mutation (P205S) in the first transmembrane domain of the CFTR gene associated with a mild cystic fibrosis phenotype. Login to comment 130 ABCC7 p.Gly85Glu 24 Friedman KJ, Blalock ML, Silverman LM. Relatively high prevalence ofthe CFTR mutations G85E and 1154insTC. Login to comment 134 ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu Relatively high prevalence ofthe CFTR mutations G85E and 1154insTC. Login to comment 137 ABCC7 p.Gly85Glu A cystic fibrosis patient who is homozygous for the G85E mutation has very mild disease. Login to comment 138 ABCC7 p.Gly85Glu 26 Skach WR. CFTR mutants G85E and G91 R insert charged residues into the first transmembrane segment and disrupt intracellular trafficking but do not alter transmembrane topology. Login to comment 140 ABCC7 p.Gly85Glu Extremely high variability of clinical presentation among CF patients carrying the missense mutation G85E. Login to comment 141 ABCC7 p.Gly85Glu A cystic fibrosis patient who is homozygous for the G85E mutation has very mild disease. Login to comment 142 ABCC7 p.Gly85Glu G85E: a pancreatic sufficiency/insufficiency homozygous for the missense mutation compound heterozygous and one Thirteen cystic fibrosis patients, 12 R Cabanas, C Soler and X Estivill C Vazquez, G Anti&#f1;olo, T Casals, J Dapena, J Elorz, J L Seculi, J Sirvent, doi: 10.1136/jmg.33.10.820 1996 33: 820-822 J Med Genet http://jmg.bmj.com/content/33/10/820 Updated information and services can be found at: These include: service Email alerting box at the top right corner of the online article. Login to comment 143 ABCC7 p.Gly85Glu 28 Kerem E, Nissim M, Argaman Z, et al. Extremely high variability of clinical presentation among CF patients carrying the missense mutation G85E. Login to comment 145 ABCC7 p.Gly85Glu G85E: a pancreatic sufficiency/insufficiency homozygous for the missense mutation compound heterozygous and one Thirteen cystic fibrosis patients, 12 http://jmg.bmj.com/content/33/10/820 Updated information and services can be found at: These include: References http://jmg.bmj.com/content/33/10/820#related-urls Article cited in: service Email alerting the box at the top right corner of the online article. Login to comment