Bone dysplasias are a group of rare
hereditary diseases, with up to 436 disease types. Perinatal diagnosis is clinically important for adequate personalized management and counseling. There are no reports focused on pathogenic variants of
bone dysplasias in the general population. In this study, we focused on autosomal recessive
bone dysplasias. We identified pathogenic variants using whole-genome reference panel data from 3552 Japanese individuals. For the first time, we were able to estimate the carrier frequencies and the proportions of potential patients. For autosomal recessive
bone dysplasias, we detected 198 pathogenic variants of 54 causative genes. We estimated the variant carrier frequencies and the proportions of potential patients with variants associated with four clinically important
bone dysplasias:
osteogenesis imperfecta (OI),
hypophosphatasia (
HPP),
asphyxiating thoracic dysplasia (ATD), and
Ellis-van Creveld syndrome (EvC). The proportions of potential patients with OI, ATD, and EvC based on pathogenic variants classified as "pathogenic" and "likely pathogenic" by InterVar were closer to the reported incidence rates in Japanese subjects. Furthermore, the proportions of potential patients with
HPP variants classified as "pathogenic" and "likely pathogenic" in InterVar and "pathogenic" in ClinVar were closer to the reported incidence rates. For
bone dysplasia, the findings of this study will provide a better understanding of the variant types and frequencies in the Japanese general population, and should be useful for clinical diagnosis, genetic counseling, and
personalized medicine.