Missense mutation in the PAX6 gene can cause a complex mild variable phenotype predominated by concomitant strabismus.

Purpose We aimed to reveal the underlying genetic defect in a multigenerational Chinese family with autosomal dominant concomitant strabismus complicated by multiple ocular developmental abnormalities. Methods Comprehensive ophthalmic examinations were performed in 14 patients and 24 healthy family members. Whole exome sequencing was performed, and Sanger sequencing was used to confirm the probable mutation in all the family members. Results Concomitant strabismus was the predominant phenotype in the affected family members, although the patients also exhibited variable phenotypes, including nystagmus, mild iris abnormalities, myopia, cataract, and coloboma. An R208W mutation in PAX6 was identified as the pathogenic mutation in the affected family members. Conclusions We recommend considering PAX6 as a candidate gene in the diagnostic screen for familial concomitant strabismus in order to avoid missed diagnosis of the mild ocular abnormalities. Careful examinations of mild ocular phenotypes are necessary for an accurate diagnosis of varied ocular abnormalities in the families with the PAX6 mutation, and proper diagnosis can facilitate genetic and clinical counseling for affected patients.