Estimating the age of the most common Italian GRN mutation: walking back to Canossa times.

摘要: Mutations in the progranulin gene (GRN) were first implicated frontotemporal lobar degeneration 2006. The GRN p.Leu271LeufsX10 mutation is one of most common mutations worldwide. To gain further insight into origin this Italy, we performed a haplotype sharing analysis (32 families, residents Lombardy) and refined dating. We showed that almost all families (30/32) can be traced to single founder. estimated age using different methods population growth rates both for Italy Lombardy. Using DMLE, dated Middle Ages, at turn millennium (phased only, Italy: 39 Lombardy: 32 generations ago; 45 Lombardy 38 ago). Mutation dating was slightly postdated Estiage only: 15 families: 20 generation From translational perspective, targeting carriers offers unique model test disease-modifying drugs clinical trials.