A family of fuchs endothelial corneal dystrophy and anterior polar cataract with an analysis of whole exome sequencing

Our aim was to introduce a family affected by this rare phenotype, and perform the whole exome sequencing (WES) to explore the potential candidate genes causing the disorders.

A five-generation family including five patients affected by FECD with APC, and nine patients suffered from only FECD was recruited from the First Affiliated Hospital of Harbin Medical University. All participants received ophthalmic examinations. Eight family members were selected to perform WES with a bioinformatics analysis and genome-wide linkage analysis. The candidate genes were identified by polymerase chain reaction (PCR) and Sanger sequencing.

Patients in this family had FECD as the common feature. The proband (a 65-year-old female) was affected by FECD and APC in both eyes, with epithelial bullae in the left eye. Slit-lamp, specular, and confocal microscope and OCT images showed guttae more serious in the central cornea than the peripheral area, confirming the diagnosis of FECD. In this family, most corneal guttae was bilateral with an almost equal degree of progression in the Descemet membrane, APC was found around the age of 10, perhaps even earlier. According to the analysis of bioinformatics analysis, two candidate genes were found and confirmed by PCR and Sanger sequencing, but could not achieve genotype-phenotype co-segregation in the family.

We introduced a family of FECD with APC, with no known causative gene found by WES, inferring that there may be a novel gene-locus in the non-coding regions of genome, which needs further study by WGS. The contribution of this study was to exclude the possibility of the rare phenotype pathogenic site in exome and narrow the scope of pathogenic genes.