%0 Journal Article %T Two New Variants in FYCO1 Are Responsible for Autosomal Recessive Congenital Cataract in Iranian Population %J Cell Journal (Yakhteh) %I Royan Institute, Iranian Academic Center for Education Culture and Research (ACECR) %Z 2228-5806 %A Shirzadeh, Ebrahim %A Piryaei, Fahimeh %A Naddaf, Hanieh %A Barabadi, Zahra %D 2022 %\ 09/01/2022 %V 24 %N 9 %P 546-551 %! Two New Variants in FYCO1 Are Responsible for Autosomal Recessive Congenital Cataract in Iranian Population %K Congenital Cataract %K FYCO1 %K Mutation %K Sanger sequencing %K Whole Exome Sequencing %R 10.22074/cellj.2022.8116 %X The purpose of this experimental study was to investigate the genetic etiology of congenital cataract (CC) manifestingan autosomal recessive pattern of inheritance in four Iranian families. Affected individuals and their normal first-degreerelatives in each family were included in the present study. The genomic DNA of the blood samples was extractedfrom 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. Twodifferent mutations were detected in the FYCO1 gene encoding FYVE and coiled-coil domain-containing protein. Apreviously 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 otherfamilies. On the other hand, accompanying the c.265C>T mutation, the presence of the c.267C>A polymorphism leadsto a premature stop codon. In-Silico Analysis of FYCO1 protein demonstrated that RUN domain will be interruptedso that the large part of functional protein will be eliminated due to this novel variant. FYCO1 has been proved to beinvolved in human lens development and transparency. Its mutations, therefore, result in CC. Herein, we reported thefirst autosomal recessive CC patients with c.265C>T (p.Arg89Cys) or c.[265C>T;267C>A] variant in Iranian populationfor the FYCO1 gene. FYCO1 mutations could be tracked for preventive objectives or even be targeted as therapeuticcandidates via treatment approaches in the future. %U https://www.celljournal.org/article_253335_f170cedf4b0d71be0041ec4f53667c0f.pdf