BIOMAT Database Logo BIOMAT Database Logo

A novel exon in the cystic fibrosis transmembrane conductance regulator gene activated by the nonsense mutation E92X in airway epithelial cells of patients with cystic fibrosis. 1994

K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
Abteilung für Humangenetik, Medizinische Hochschule, Hannover, Germany.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We report on a novel nonsense mutation that leads to exon skipping and the activation of a cryptic exon. Screening of genomic DNA from 700 German patients with CF uncovered four cases with the nonsense mutation E92X, a G-->T transversion that creates a termination codon and affects the first base of exon 4 of the CFTR gene. Lymphocyte RNA of two CF patients heterozygous for E92X was found to contain the wild type sequence and a differentially spliced isoform lacking exon 4. In RNA derived from nasal epithelial cells of E92X patients, a third fragment of longer size was observed. Sequencing revealed the presence of E92X and an additional 183-bp fragment, inserted between exons 3 and 4. The 183-bp sequence was mapped to intron 3 of the CFTR gene. It is flanked by acceptor and donor splice sites. We conclude that the 183-bp fragment in intron 3 is a cryptic CFTR exon that can be activated in epithelial cells by the presence of the E92X mutation. E92X abolishes correctly spliced CFTR mRNA and leads to severe cystic fibrosis.

UI MeSH Term Description Entries
D008297 Male Males
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009297 Nasal Mucosa The mucous lining of the NASAL CAVITY, including lining of the nostril (vestibule) and the OLFACTORY MUCOSA. Nasal mucosa consists of ciliated cells, GOBLET CELLS, brush cells, small granule cells, basal cells (STEM CELLS) and glands containing both mucous and serous cells. Nasal Epithelium,Schneiderian Membrane,Epithelium, Nasal,Membrane, Schneiderian,Mucosa, Nasal
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D003550 Cystic Fibrosis An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION. Mucoviscidosis,Cystic Fibrosis of Pancreas,Fibrocystic Disease of Pancreas,Pancreatic Cystic Fibrosis,Pulmonary Cystic Fibrosis,Cystic Fibrosis, Pancreatic,Cystic Fibrosis, Pulmonary,Fibrosis, Cystic,Pancreas Fibrocystic Disease,Pancreas Fibrocystic Diseases
D005091 Exons The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA. Mini-Exon,Exon,Mini Exon,Mini-Exons
D005260 Female Females

Related Publications

K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
A novel nonsense mutation, S466Xa in exon 10 of the cystic fibrosis transmembrane conductance regulator gene.
January 1996, Human mutation,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
A novel nonsense mutation, S434X, in exon 9 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
August 1999, Human mutation,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
A novel nonsense mutation, W846XI (amber termination), in exon 14a of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
July 1993, Human molecular genetics,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
Identification of a novel nonsense mutation (L88X) in exon 3 of the cystic fibrosis transmembrane conductance regulator gene in a native Korean cystic fibrosis chromosome.
January 1992, Human mutation,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
A nonsense mutation (R1158X) and a splicing mutation (3849 + 4A----G) in exon 19 of the cystic fibrosis transmembrane conductance regulator gene.
February 1992, Genomics,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
A missense mutation (F87L) in exon 3 of the cystic fibrosis transmembrane conductance regulator gene.
January 1994, Human mutation,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
A novel missense mutation in exon 16 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene identified in CBAVD patients.
January 1996, Human mutation,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
The cystic fibrosis transmembrane conductance regulator activates aquaporin 3 in airway epithelial cells.
April 1999, The Journal of biological chemistry,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
A new missense mutation (R1283M) in exon 20 of the cystic fibrosis transmembrane conductance regulator gene.
May 1992, Human molecular genetics,
K Will, and T Dörk, and M Stuhrmann, and T Meitinger, and R Bertele-Harms, and B Tümmler, and J Schmidtke
Up-regulation of AMP-activated kinase by dysfunctional cystic fibrosis transmembrane conductance regulator in cystic fibrosis airway epithelial cells mitigates excessive inflammation.
February 2006, The Journal of biological chemistry,
Copied contents to your clipboard!