Two New Variants in FYCO1 Are Responsible for Autosomal Recessive Congenital Cataract in Iranian Population.

The purpose of this experimental study was to investigate the genetic etiology of congenital cataract (CC) manifesting an autosomal recessive pattern of inheritance in four Iranian families. Affected individuals and their normal first-degree relatives in each family were included in the present study. The genomic DNA of the blood samples was extracted from all participants, and one affected member belonging to each family was subjected to Whole Exome Sequencing (WES). Using bidirectional Sanger sequencing, the identified variants were validated by co-segregation analysis. Two different mutations were detected in the FYCO1 gene encoding FYVE and coiled-coil domain-containing protein. A previously reported missense mutation, c.265C>T (p.Arg89Cys), was found in one Iranian family for the first time, and a combination of two variants in a single codon, c.[265C>T;267C>A] (p.Arg89X), was identified in the three other families. On the other hand, accompanying the c.265C>T mutation, the presence of the c.267C>A polymorphism leads to a premature stop codon. In-Silico Analysis of FYCO1 protein demonstrated that RUN domain will be interrupted so that the large part of functional protein will be eliminated due to this novel variant. FYCO1 has been proved to be involved in human lens development and transparency. Its mutations, therefore, result in CC. Herein, we reported the first autosomal recessive CC patients with c.265C>T (p.Arg89Cys) or c.[265C>T;267C>A] variant in Iranian population for the