Cystic Fibrosis - History

History

It is supposed that CF appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment. Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier. Indeed, literature from Germany and Switzerland in the 18th century warned Wehe dem Kind, das beim Kuß auf die Stirn salzig schmekt, er ist verhext und muss bald sterbe or "Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die," recognizing the association between the salt loss in CF and illness.

In the 19th century, Carl von Rokitansky described a case of fetal death with meconium peritonitis, a complication of meconium ileus associated with cystic fibrosis. Meconium ileus was first described in 1905 by Karl Landsteiner. In 1936, Guido Fanconi published a paper describing a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis.

In 1938 Dorothy Hansine Andersen published an article, "Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study," in the American Journal of Diseases of Children. She was the first to describe the characteristic cystic fibrosis of the pancreas and to correlate it with the lung and intestinal disease prominent in CF. She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952 Paul di Sant' Agnese discovered abnormalities in sweat electrolytes; a sweat test was developed and improved over the next decade.

The first linkage between CF and another marker (Paroxonase) was found in 1985, indicating that only one locus exists for CF Hans Eiberg. In 1988 the first mutation for CF, ΔF508 was discovered by Francis Collins, Lap-Chee Tsui and John R. Riordan on the seventh chromosome. Subsequent research has found over 1,000 different mutations that cause CF.

Because mutations in the CFTR gene are typically small, classical genetics techniques had been unable to accurately pinpoint the mutated gene. Using protein markers, gene-linkage studies were able to map the mutation to chromosome 7. Chromosome-walking and -jumping techniques were then used to identify and sequence the gene. In 1989 Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children in Toronto that discovered the gene responsible for CF. Cystic fibrosis represents the first genetic disorder elucidated strictly by the process of reverse genetics.