On November 10, 2021, Professor Han Dong's team achieved an important milestone in their research on pathogenic genes and rare phenotypes of tooth agenesis. An article entitled: “Rare phenotype: Hand preaxial polydactyly associated with LRP6-related tooth agenesis in humans”, was published in a NATURE Partner Journal - NPJ Genomic Medicine. This is the first report of a rare phenotype, hand preaxial polydactyly, in tooth agenesis patients with novel pathogenic mutations of LRP6. Professor Han Dong from the Department of Prosthodontics is the corresponding lead author of this paper. Dr. Zhang Liutao, a graduate student from the eight-year program, and Dr. Yu Miao, a research assistant, are the co-first authors of this article.

In this study, the molecular genetics and clinical phenotypic characteristics of tooth agenesis among families with oligodontia were analyzed by whole exome sequencing. We reported a novel autosomal dominant LRP6 heterozygous mutation (c.2840T>C;p.Met947Thr) in a family with tooth agenesis and hand polydactyly, as well as another two LRP6 heterozygous mutation in families with non-syndromic tooth agenesis. Analysis of the pattern of LRP6-related tooth agenesis demonstrated that the maxillary lateral incisor was the most affected (88.46%). We observed hand thumb polydactyly in a family with tooth agenesis caused by LRP6 mutation, which broadened the phenotypic spectrum of LRP6‐related disorders. Our findings thus facilitated early genetic diagnosis and perinatal counseling, and provided new evidence for the clinical diagnosis and classification of tooth agenesis, as well as improved our understanding of pathogenesis, which could lead to the ultimate realization of "gene precision therapy" for this disease.

Professor Han Dong's research group has been committed to investigating the molecular mechanisms and clinical translational applications of tooth agenesis for more than 10 years.

Fig. 1. The rare phenotype of Hand preaxial polydactyly was reported in patients with tooth agenesis carrying novel pathogenic mutations of LRP6

Fig. 2. Structural modeling of the wild-type and mutated functional domains of LRP6 protein.