Homozygosity Mapping and Targeted Sanger Sequencing Identifies Three Novel CRB1 (Cumbs homologue 1) Mutations in Iranian Retinal Degeneration Families

Authors
Mohammad Ghofrani 1
Mahin Yahyaei 1
Han G. Brunner 2
Frans P.M. Cremers 2
Morteza Movasat 3
Muhammad Imran Khan 4
Mohammad Keramatipour 5
1 Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
2 Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
3 Eye Research Center, Tehran University of Medical Sciences, Farabi Eye Hospital, Tehran, Iran
4 Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
5 Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
10.18869/acadpub.ibj.21.5.294
Abstract
Background: Inherited retinal diseases (IRDs) are a group of genetic disorders with high degrees of clinical, genetic and allelic heterogeneity. IRDs generally show progressive retinal cell death resulting in gradual vision loss. IRDs constitute a broad spectrum of disorders including retinitis pigmentosa and Leber congenital amaurosis. In this study, we performed genotyping studies to identify the underlying mutations in three Iranian families. Methods: Having employed homozygosity mapping and Sanger sequencing, we identified the underlying mutations in the crumbs homologue 1 gene. The CRB1 protein is a part of a macromolecular complex with a vital role in retinal cell polarity, morphogenesis, and maintenance. Results: We identified a novel homozygous variant (c.1053_1061del; p.Gly352_Cys354del) in one family, a combination of a novel (c.2086T>C; p.Cys696Arg) and a known variant (c.2234C>T, p.Thr745Met) in another family and a homozygous novel variant (c.3090T>A; p.Asn1030Lys) in a third family. Conclusion: This study shows that mutations in CRB1 are relatively common in Iranian non-syndromic IRD patients.
Keywords
Retinal degeneration
Retinitis pigmentosa
Leber congenital amaurosis
Mutation
Iran