Trio-based exome sequencing arrests de novo mutations in early-onset high myopia

Abstract

Significance Because preschool children encounter fewer risks from environmental pressures, we propose that the condition of early-onset high myopia (EOHM) is driven by a genetic predisposition more than by environmental factors. In this study, we recruited 18 familial trios to decipher the genetic predisposition using whole-exome sequencing. We identified a cluster of unique genes linked to EOHM, as well as mutations in the reported genes. Notably, we showed that both rare inherited mutations and de novo mutations significantly contributed to EOHM. Expression profiling in ocular tissues and mutant mouse phenotyping demonstrated the pathogenicity of mutations in a unique gene, BSG . Our results provide insights into the genetic basis and molecular mechanisms of childhood high myopia.