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

Document Type : Short Communication


1 Department of Ophthalmology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

2 Department of Molecular Medicine and Genetics, Research Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

3 Core facility of Hamadan University of Medical Sciences, Hamadan, Iran

4 6517838696, Department of Tissue Engineering, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

5 School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran


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 FYCO1 gene. FYCO1 mutations could be tracked for preventive objectives or even be targeted as therapeutic
candidates via treatment approaches in the future.


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