Familial Exudative Vitreoretinopathy-Like Retinal Findings in Adams-Oliver Syndrome Type 2.

Background: This study investigated the clinical characteristics and the genotype-phenotype correlation of DOCK6-associated autosomal recessive Adams-Oliver Syndrome in a large cohort of familial exudative vitreoretinopathy patients.

Methods: Comprehensive ocular examinations were conducted on probands and their family members. Whole-exome sequencing (WES) was performed on the probands, with Sanger sequencing validation for family members. In vitro experiments validated copy number variation (CNV) and splice-site mutations.

Results: A total of 642 families with FEVR phenotypes were included, leading to the identification of seven probands with biallelic pathogenic DOCK6 mutations, corresponding to a prevalence of 1.09%. Thirteen mutation sites were identified, including seven frameshift mutations, four splice mutations, one CNV, and one nonsense mutation, indicating the pathogenic mechanism of DOCK6 in FEVR is more likely due to functional loss. Among the 14 eyes of the seven probands, five eyes (35.71%) and four eyes (28.57%) exhibited total retinal detachment and retinal folds, respectively.

Conclusions: Biallelic DOCK6 mutations represent a genetic cause of FEVR. These pathogenic mutations typically result in loss of function, leading to severe ocular and systemic manifestations. These findings highlight the importance of considering DOCK6 mutations in patients presenting with atypical or severe FEVR phenotypes.