LRP2 and Cowden syndrome 1: In summary, based on genome-wide linkage analysis, WES, and pathogenic analysis, we mapped non-syndromic CS to a novel locus on chromosome 2q22.3-2q32.1 and identified the rare heterozygous variant c.335A > G (p.Q112R) and novel heterozygous variants c.7274A > G, (p.D2425G) in LRP2. To the best of our knowledge, our study is the first report that LRP2 is a genetic cause of non-syndromic CS, expanding the phenotypic spectrum of LRP2 mutations.