en Molecular Genetics & Genomics Molecular Genetics & Genomics مقاله موردی Case Report <strong>Background: </strong>Leber congenital amaurosis (LCA) is a rare inherited retinal disease causing severe visual impairment in infancy. It has been reported that 9-15% of LCA cases have mutations in <em>CRB1</em> gene. The complex of CRB1 protein with other associated proteins affects the determination of cell polarity, orientation, and morphogenesis of photoreceptors. Here, we report three novel pathogenic variants in <em>CRB1</em> gene and then briefly review the types, prevalence, and correlation of reported mutations in <em>CRB1 </em>gene. <strong>Methods: </strong>Whole exome sequencing and targeted gene panel were employed. Then validation in the patient and segregation analysis in affected and unaffected members was performed. <strong>Results:</strong> Our detected novel pathogenic variants (p.Glu703*, c.2128+1G>A and p.Ser758SerfsX33) in <em>CRB1</em> gene were validated by Sanger sequencing. Segregation analysis confirmed the inheritance pattern of the pathogenic variants. <strong>Conclusion: </strong>Our findings show that emerging the next-generation sequencing-based techniques is very efficient in identifying causative variants in disorders with locus heterogeneity.&nbsp; CRB1, Leber congenital amaurosis, Retinal dystrophies, Whole exome sequencing 362 368 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1-762&slc_lang=en&sid=1 Mohammad Saberi No Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Zahra Golchehre No Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Arezou Karamzade No Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mona Entezam 0000-0002-2608-464X No Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Yeganeh Eshaghkhani No Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Elaheh Alavinejad No Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Hassan Khojasteh Jafari 0000-0001-9407-5764 No Farabi Eye Hospital, Tehran, Iran Mohammad Keramatipour 0000-0002-5803-4209 Yes Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran