Global distribution of Fatal familial insomnia: founder or recurrent mutations

Excerpt

The mechanisms of geographic spread of hereditary disorders through predominantly founder effect or predominantly recurrent mutational events is not only of historic significance; it is important for understanding molecular mechanisms of disease spread and may ultimately influence the selection of methods for disease prevention. As reported in the recent issue of the Journal, Rodriguez-Martinez et al. [1] carried out a haplotype analysis of the PRNP D178N genetic variant associated with Fatal familial insomnia (FFI) by using seven single nucleotide polymorphisms (SNPs) for identification of disease haplotypes in 38 cases (27 probands) that occurred in three European countries. The study reports two founder FFI haplotypes. All Spanish cases and one family from the Tuscany region in Italy share a common haplotype, and all nine German patients and an Italian family from Veneto region share the second haplotype. The likelihood G goodness-of-fit test shows a difference in haplotype frequency distribution between Spanish FFI cases and Spanish controls. Based on these results, the authors conclude that two independent ancient PRNP D178N mutational events are responsible for most of the current FFI cases in Europe. …