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

Ghofrani, Mohammad; Yahyaei, Mahin; Brunner, Han G.; Cremers, Frans P.M.; Movasat, Morteza; Imran Khan, Muhammad; Keramatipour, Mohammad

doi:10.18869/acadpub.ibj.21.5.294

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