title: Complex cystic fibrosis allele R334W-R1158X results in reduced levels of correctly processed mRNA in a pancreatic sufficient patient.
abstract: CFTR alleles containing two mutations have been very rarely found in cystic fibrosis (CF) patients. They provide an opportunity to study the effect of two in cis-interacting gene defects on gene expression. Here, we describe a three-generation CF family with a complex CFTR allele that has not been previously described, containing the missense mutation R334W in exon 7 and the nonsense mutation R1158X in exon 19. Lymphocyte RNA analysis showed that (1) the mRNA corresponding to the complex allele is present although at markedly reduced levels; and (2) the nonsense mutation does not lead to detectable skipping of exon 19. The clinical picture of the patients with the genotype R334W-R1158X/delta F508 is characterized by pancreatic sufficiency and an atypical course of the disease.
authors.affiliation: Departamento de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Duarte
authors.forename: M
authors.initials: M
authors.lastname: Amaral
authors.forename: C
authors.initials: C
authors.lastname: Barreto
authors.forename: P
authors.initials: P
authors.lastname: Pacheco
authors.forename: J
authors.initials: J
authors.lastname: Lavinha
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010179:Pancreas / Q000503:physiopathology*; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
chemical_list: C505032:CFTR protein, human; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator