title: Thirteen cystic fibrosis patients, 12 compound heterozygous and one homozygous for the missense mutation G85E: a pancreatic sufficiency/insufficiency mutation with variable clinical presentation.
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. G85E accounts for about 1% of Spanish CF alleles. One patient was homozygous G85E/G85E and the rest were compound heterozygotes for G85E and other mutations (delta F508 nine patients, delta I507 two patients, and 712-1G > T one patient). The characteristics of the pooled G85E/any mutation group were compared with those of 30 delta F508 homozygotes. 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 < 0.01). The G85E homozygote was pancreatic sufficient. Sweat sodium levels were slightly higher, and salt loss related problems more frequent, in the G85E/any group. Two of the G85E patients died of respiratory failure aged 6 and 14 years. Striking discordance in the phenotype was observed in two pairs of sibs, one of them dizygotic twins, suggesting that factors, genetic and environmental, other than CFTR genotype are important in determining CF phenotype.
authors.affiliation: Cystic Fibrosis Unit, Hospital Infantil de Cruces, Pais Vasco, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Vazquez
authors.forename: G
authors.initials: G
authors.lastname: Antiñolo
authors.forename: T
authors.initials: T
authors.lastname: Casals
authors.forename: J
authors.initials: J
authors.lastname: Dapena
authors.forename: J
authors.initials: J
authors.lastname: Elorz
authors.forename: J L
authors.initials: JL
authors.lastname: Seculi
authors.forename: J
authors.initials: J
authors.lastname: Sirvent
authors.forename: R
authors.initials: R
authors.lastname: Cabanas
authors.forename: C
authors.initials: C
authors.lastname: Soler
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D010188:Exocrine Pancreatic Insufficiency / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator