Novel variants identified in a three‑generation family with concomitant exotropia

Concomitant exotropia is a condition where there is a misalignment between both eyes, which is more prevalent in Asians than in Caucasians. It is an eye disease related to the neural development of binocular vision and eye movement control. Studies have indicated that genetic factors contribute to the development of concomitant exotropia; however, the underlying mutations have not been thoroughly investigated to date. In the present study, whole-exome sequencing was performed in a three-generation family with concomitant exotropia. In the proband and the proband's father, bioinformatics analyses identified a duplication of the genomic region spanning genes PCDHA1-7 and a heterozygous mutation c.3775G>A (p.A1259T) of the COL3A1 gene, which is located in the conserved COLFI domain and leads to decreased stability of the encoded protein product. Furthermore, a deletion of amino acid S165 in the gene NCOA7 was discovered in the family members, including the proband, the proband's mother and maternal grandfather. S165 was predicted to be a conserved phosphokinase site of CK1/VRK and CK1/CK1. The genes in which these variants reside are all involved in cortical neuronal development. The present study reveals novel variants of concomitant exotropia and suggests that aberrant cortical neuronal development may contribute to the origin of concomitant strabismus.