Thirty Years of Research into Rendu-Osler-Weber Disease in France: Historical Demography, Population Genetics and Molecular Biology

After thirty years of research into Rendu-Osler-Weber disease, the authors review the contributions of the three successive approaches used to analyse this rare genetic disorder. First, historical demography sees patients as markers of past migration and population transfers. Starting out from a cluster of cases straddling the Ain and Jura départements, the history of this population group was reconstituted on the basis of civil records, and their migration to other parts of France was studied by looking for family ties between the initial group and the cases observed elsewhere in the country. Second, epidemiology and population genetics give estimates of prevalence by département that are higher than those initially predicted in 1977, the start year of this study. They also provide statistical tools to test hypotheses of a single or multiple origin for the disease by looking for a common ancestor among affected families. Last, molecular biology provides a means to identify the genes responsible for the disease and their various mutations, thus confirming the existence of several different origins. Following the articles published in 1984 and 1989, (Plauchu and Bideau, 1984; Bideau et al., 1989), this article concludes a key phase in the study of Rendu-Osler-Weber disease in France, and opens the way for future international comparisons. [PUBLICATION ABSTRACT]