The cystic fibrosis defect approached from different angles — new perspectives on the gene, the chloride channel, diagnosis and therapy

Abstract

Abstract. The search for the basic defect in cystic fibrosis (CF) has reached a decisive stage since the recent identification of the responsible gene. Electrophysiological and biochemical research had defined the CF defect as a dysregulation of epithelial chloride channels. The putative protein product of the now identified gene shares properties with other known transport proteins, but it is not necessarily itself a chloride channel protein. Elucidation of the primary cellular defect will certainly have important aetiological and hopefully therapeutic implications. The identification of the major gene mutation already has significant consequences for genetic counselling and prenatal diagnosis. Heterozygote detection at the population level awaits identification of the probably heterogenous mutations on about 30% of the CF chromosomes. At present, about 50% of CF patients are homozygous for the recently identified major CF mutation.

The effect of synthetic surfactant Exosurf on gene transfer in mouse lung in vivo

“…This destruction is a major cause of morbidity and mortality in afflicted patients. 1 The delivery of genes to the airway is aided by the relative accessibility of the bronchial tree through inhalation, and this route of administration essentially limits transgene expression to the bronchial epithelium and alveoli. Animal models of bronchial gene transfer have proved crucial to the evaluation of the feasibility, efficiency and safety of various therapeutic strategies.…”

Lung Gene Therapy: In Vivo Adenovirus-Mediated Gene Transfer to Rhesus Monkey Airway Epithelium

“…CYSTIC FIBROSIS (CF) is the most common lethal autosomal recessive disorder in the Caucasian population, with a disease frequency of 1 in 2,500 live births on average (Halley et al, 1990). CF is characterized clinically by chronic pulmonary disease, pancreatic insufficiency, and an increase in the concentration of sweat electrolytes.…”

Genotype/Phenotype Association in Cystic Fibrosis: Analyses of the ΔF508, R553X, and 3905insT Mutations

“…(Pediatr Res 32: 175-178, 1992) Abbreviations CF is the most commo n severe autosomal recessive genetic disorder in Caucasian populations, with an incidence of about 1 in 2000 live births, implying a carrier frequency of about 1 in 22. The fundamental defect in CF appears to be a dysfunction of exocrine gland epithelia leading to abnormal secretions that cause obstruction of organ ducts (1). CF is clinically characterized by chronic airway infection and bronchiectasis, pancreatic insufficiency with malabsorpti on and impaired growth, abnormalities of the intestine (meconium ileus) and the reprodu ctive organs (azoospermia, low female fertility), and elevated sweat chloride concent rations (2).…”