Rare phenotype: Hand preaxial polydactyly associated with LRP6-related tooth agenesis in humans

Low-density lipoprotein receptor-related protein 6 (LRP6) is a pathogenic gene of selective tooth agenesis-7 (OMIM#616724). Although the malformation of the digits and fore- and hindlimbs has been reported in Lrp6-deficient mice, it has been rarely discovered in humans with LRP6 mutations. Here, we demonstrate an unreported autosomal dominant LRP6 heterozygous mutation (c.2840 T > C;p.Met947Thr) in a tooth agenesis family with hand polydactyly, and another unreported autosomal dominant LRP6 heterozygous mutation (c.1154 G > C;p.Arg385Pro) in a non-syndromic tooth agenesis family. Bioinformatic prediction demonstrated the deleterious effects of the mutations, and LRP6 structure changes suggested the corresponding functional impairments. Analysis on the pattern of LRP6-related tooth agenesis demonstrated the maxillary lateral incisor was the most affected. Our study report that LRP6 mutation might be associated with hand preaxial polydactyly in humans, which broaden the phenotypic spectrum of LRP6-related disorders, and provide valuable information on the characteristics of LRP6-related tooth agenesis.