{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:15:09Z","timestamp":1780571709187,"version":"3.54.1"},"reference-count":34,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,9,1]]},"abstract":"<jats:p>Objective.\u2003Cystic fibrosis (CF) has variable clinical presentation. Disease severity is partially associated with the type of mutation. The aim of this study was to report genotype-phenotype analysis of the G85E mutation.<\/jats:p>\n               <jats:p>Patients.\u2003The phenotype of 12 patients (8 were from the same extended family, and 5 of them were siblings from 2 families) carrying at least one copy of the G85E mutation was evaluated and compared with the phenotype of 40 patients carrying the two severe mutations, W1282X and\/or \u0394F508 (group 1), and with 20 patients carrying the splicing mutation, 3849+10kb C-&amp;gt;T, which was found to be associated with milder disease (group 2).<\/jats:p>\n               <jats:p>Results.\u2003A high phenotypic variability was found among the patients carrying the G85E mutation. This high variability was found among patients carrying the same genotype and among siblings. All the studied chromosomes carrying the G85E mutation had the 7T variant in the polythymidine tract at the branch\/acceptor site in intron 8. Of the G85E patients, 25% had pancreatic sufficiency and none had meconium ileus, compared with 0% and 32%, respectively, of patients from group 1, and 80% and 0%, respectively, from group 2. Two patients carrying the G85E mutation had sweat chloride levels &amp;lt;60 mmol\/L whereas all the others had typically elevated levels &amp;gt;80 mmol\/L. Compared with group 2, patients carrying the G85E mutation were diagnosed at an earlier age and had higher sweat chloride levels, with mean values similar to group 1 but significantly more variable. Forced expiratory volume in 1 second (FEV1) was similar in the three groups, with no differences in the slope or in age-adjusted mean values of FEV1. The levels of transcripts lacking exon 9 transcribed from the G85E allele measured in 3 patients were 55%, 49%, and 35% and their FEV1 values were 82%, 83%, and 50% predicated, respectively.<\/jats:p>\n               <jats:p>Conclusions.\u2003The G85E mutation shows variable clinical presentation in all clinical parameters. This variability could be seen among patients carrying on the other chromosome the same CFTR mutation, and also among siblings. This variability is not associated with the level of exon 9 skipping. Thus, the G85E mutation cannot be classified either as a severe or as a mild mutation.<\/jats:p>","DOI":"10.1542\/peds.100.3.e5","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:40:17Z","timestamp":1092440417000},"page":"e5-e5","source":"Crossref","is-referenced-by-count":19,"title":["A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype"],"prefix":"10.1542","volume":"100","author":[{"given":"Eitan","family":"Kerem","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Cystic Fibrosis (CF) Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malka","family":"Nissim-Rafinia","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hebrew University, Jerusalem; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Argaman","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Cystic Fibrosis (CF) Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Augarten","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, CF Clinic, Chaim Sheba Medical Center, Tel Hashomer, Israel; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Bentur","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, CF Clinic, Rambam Medical Center, Haifa; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aharon","family":"Klar","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Bikur Cholim Hospital, Jerusalem, Israel; and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaacov","family":"Yahav","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, CF Clinic, Chaim Sheba Medical Center, Tel Hashomer, Israel; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Szeinberg","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, CF Clinic, Chaim Sheba Medical Center, Tel Hashomer, Israel; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornit","family":"Hiba","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hebrew University, Jerusalem; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Branski","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Cystic Fibrosis (CF) Clinic, Shaare Zedek Medical Center, Jerusalem, Israel; and the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Corey","sequence":"additional","affiliation":[{"name":"Research Institute, Hospital for Sick Children, Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batsheva","family":"Kerem","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hebrew University, Jerusalem; the"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[1997,9,1]]},"reference":[{"key":"2021121023365237800_B1"},{"key":"2021121023365237800_B2","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1056\/NEJM199011293232203","article-title":"The relationship between genotype and phenotype in cystic fibrosis\u2014analysis of the most common mutation (\u0394F508).","volume":"323","author":"Kerem","year":"1990","journal-title":"N Engl J Med"},{"key":"2021121023365237800_B3","first-page":"222","article-title":"Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease.","volume":"50","author":"Shoshani","year":"1992","journal-title":"Am J Hum Genet"},{"key":"2021121023365237800_B4","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/BF00221957","article-title":"Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR) gene.","volume":"89","author":"Osborn","year":"1992","journal-title":"Hum Genet"},{"key":"2021121023365237800_B5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1203\/00006450-199208000-00010","article-title":"Genotype-phenotype association in cystic fibrosis: analysis of the \u0394F508, R553X and 3905insT mutations.","volume":"32","author":"Liechti-Gallati","year":"1992","journal-title":"Pediatr Res"},{"key":"2021121023365237800_B6","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1056\/NEJM199310283291804","article-title":"Correlation between genotype and phenotype in patients with cystic fibrosis.","volume":"329","author":"The Cystic Fibrosis Genotype-Phenotype Consortium","year":"1993","journal-title":"N Engl J Med"},{"key":"2021121023365237800_B7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0140-6736(93)91885-P","article-title":"Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849+10kb C-&gt;T mutation.","volume":"342","author":"Augarten","year":"1993","journal-title":"Lancet"},{"key":"2021121023365237800_B8","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1056\/NEJM199410133311503","article-title":"A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations.","volume":"331","author":"Highsmith","year":"1994","journal-title":"N Engl J Med"},{"key":"2021121023365237800_B9","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/humu.1380030405","article-title":"Cystic fibrosis patients from the Black Sea region: the 1677delTA mutation.","volume":"3","author":"Angelicheva","year":"1994","journal-title":"Hum Mutat"},{"key":"2021121023365237800_B10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/jmg.31.2.159","article-title":"Association of 1078delT cystic fibrosis mutation with severe disease.","volume":"31","author":"Moullier","year":"1994","journal-title":"J Med Genet"},{"key":"2021121023365237800_B11","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/0140-6736(90)92566-Z","article-title":"Independent genetic determinants of pancreatic and pulmonary status in cystic fibrosis.","volume":"336","author":"Santis","year":"1990","journal-title":"Lancet"},{"key":"2021121023365237800_B12","first-page":"245","article-title":"Cystic fibrosis patients bearing both the common missense mutation Gly-&gt;Asp at codon 551 and \u0394F508 mutation are clinically indistinguishable from \u0394F508 homozygotes except for decreased risk of meconium ileus.","volume":"51","author":"Hamosh","year":"1992","journal-title":"Am J Hum Genet"},{"key":"2021121023365237800_B13","first-page":"623","article-title":"A novel donor splice site in intron 11 of the CFTR gene, created a mutation 1811+1.6kbA\u2192G, produces a new exon. High frequency in Spanish cystic fibrosis chromosomes and association with severe phenotype.","volume":"56","author":"Chillon","year":"1995","journal-title":"Am J Hum Genet"},{"key":"2021121023365237800_B14","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/BF00225203","article-title":"Clinical characteristics of 16 cystic fibrosis patients with the missense mutation R334W, pancreatic insufficiency mutation with variable age of onset and interfamilial clinical differences.","volume":"95","author":"Estivill","year":"1995","journal-title":"Hum Genet"},{"key":"2021121023365237800_B15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1056\/NEJM199507133330204","article-title":"A cystic fibrosis mutation associated with mild lung disease.","volume":"333","author":"Gan","year":"1995","journal-title":"N Engl J Med"},{"key":"2021121023365237800_B16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/humu.1380060304","article-title":"Pancreatic insufficiency and pulmonary disease in German and Slavic cystic fibrosis patients with the R347P mutation.","volume":"6","author":"Varon","year":"1995","journal-title":"Hum Mut"},{"key":"2021121023365237800_B17","first-page":"1178","article-title":"Genetic determinants of exocrine pancreatic function.","volume":"50","author":"Kristidis","year":"1992","journal-title":"Am J Hum Genet"},{"key":"2021121023365237800_B18","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0888-7543(91)90504-8","article-title":"Identification of mutations in exons 1 through 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.","volume":"10","author":"Zielenski","year":"1991","journal-title":"Genomics"},{"key":"2021121023365237800_B19","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1136\/jmg.28.12.875","article-title":"A cystic fibrosis patient who is homozygous for the G85E mutation has very mild disease.","volume":"28","author":"Chalkey","year":"1991","journal-title":"J Med Genet"},{"key":"2021121023365237800_B20","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.2999980","article-title":"Enzymatic amplification of beta globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.","volume":"230","author":"Saiki","year":"1985","journal-title":"Science"},{"key":"2021121023365237800_B21","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1126\/science.2448875","article-title":"Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.","volume":"239","author":"Saiki","year":"1988","journal-title":"Science"},{"key":"2021121023365237800_B22","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/0888-7543(91)90503-7","article-title":"Genomic DNA sequences of the cystic fibrosis transmembrane conductance regulator.","volume":"10","author":"Zielenski","year":"1991","journal-title":"Genomics"},{"key":"2021121023365237800_B23","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1093\/nar\/17.3.1266","article-title":"An improved method for directly sequencing PCR amplified material using dimethyl sulphoxide.","volume":"17","author":"Winship","year":"1989","journal-title":"Nucleic Acids Res"},{"key":"2021121023365237800_B24","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF00207378","article-title":"Highly variable incidence of cystic fibrosis mutation distribution among different ethnic Jewish groups in Israel.","volume":"96","author":"Kerem","year":"1995","journal-title":"Hum Genet"},{"key":"2021121023365237800_B25","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/ng1193-274","article-title":"A mutation in CFTR produces different phenotypes depending on chromosomal background.","volume":"5","author":"Kiesewetter","year":"1993","journal-title":"Nature Genet"},{"key":"2021121023365237800_B26","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.1021\/bi00591a005","article-title":"Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.","volume":"18","author":"Chirgwin","year":"1979","journal-title":"Biochemistry"},{"key":"2021121023365237800_B27"},{"key":"2021121023365237800_B28","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1136\/adc.41.219.454","article-title":"Standards from birth to maturity for height, weight, height velocity and weight velocity: British children, 1965.","volume":"41","author":"Tanner","year":"1966","journal-title":"Arch Dis Child"},{"key":"2021121023365237800_B29","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/BF00197165","article-title":"Cystic fibrosis with three mutations in the cystic fibrosis transmembrane conductance regulator gene.","volume":"87","author":"Dork","year":"1991","journal-title":"Hum Genet"},{"key":"2021121023365237800_B30","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/humu.1380010305","article-title":"A cystic fibrosis allele encoding missense mutations in both nucleotide binding folds of the cystic fibrosis transmembrane conductance regulator.","volume":"1","author":"Kalin","year":"1993","journal-title":"Hum Mut"},{"key":"2021121023365237800_B31","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1172\/JCI115952","article-title":"Extensive posttranscriptional deletion of the coding sequences of part of nucleotide-binding fold 1 in respiratory epithelial m RNA transcripts of the cystic fibrosis transmembrane conductance regulator gene is not associated with the clinical manifestations of cystic fibrosis.","volume":"90","author":"Chu","year":"1992","journal-title":"J Clin Invest"},{"key":"2021121023365237800_B32","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/ng0293-151","article-title":"Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNA.","volume":"3","author":"Chu","year":"1993","journal-title":"Nature Genet"},{"key":"2021121023365237800_B33","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/ng1193-274","article-title":"A mutation in CFTR produces different phenotypes depending on chromosomal background.","volume":"5","author":"Kiesewetter","year":"1993","journal-title":"Nature Genet"},{"key":"2021121023365237800_B34","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/ng0396-280","article-title":"Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor.","volume":"12","author":"Rozmahel","year":"1996","journal-title":"Nature Genet"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/100\/3\/e5\/885175\/e5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/100\/3\/e5\/885175\/e5.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T08:03:32Z","timestamp":1639209812000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/100\/3\/e5\/39120\/A-Missense-Cystic-Fibrosis-Transmembrane"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,9,1]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1997,9,1]]},"published-print":{"date-parts":[[1997,9,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.100.3.e5","relation":{},"ISSN":["1098-4275","0031-4005"],"issn-type":[{"value":"1098-4275","type":"electronic"},{"value":"0031-4005","type":"print"}],"subject":[],"published":{"date-parts":[[1997,9,1]]}}}