Novel mutations in CRB1 gene identified in a chinese pedigree with retinitis pigmentosa by targeted capture and next generation sequencing.

Lan Lu,Xuyang Liu,David Lo,Yun Wang,Fen He,Xizhen Wang,Juhua Yang,Jingning Weng,Xiaohong Liu

doi:10.18632/oncotarget.12971

Abstract

PURPOSETo detect the disease-causing gene in a Chinese pedigree with autosomal-recessive retinitis pigmentosa (ARRP).METHODSAll subjects in this family underwent a complete ophthalmic examination. Targeted-capture next generation sequencing (NGS) was performed on the proband to detect variants. All variants were verified in the remaining family members by PCR amplification and Sanger sequencing.RESULTSAll the affected subjects in this pedigree were diagnosed with retinitis pigmentosa (RP). The compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations in the Crumbs homolog 1 (CRB1) gene were identified in all the affected patients but not in the unaffected individuals in this family. These mutations were inherited from their parents, respectively.CONCLUSIONThe novel compound heterozygous mutations in CRB1 were identified in a Chinese pedigree with ARRP using targeted-capture next generation sequencing. After evaluating the significant heredity and impaired protein function, the compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations are the causal genes of early onset ARRP in this pedigree. To the best of our knowledge, there is no previous report regarding the compound mutations.

Highlights

Retinitis pigmentosa (RP) is a hereditary neurodegenerative retinal disease characterized by progressive loss of photoreceptors
The novel compound heterozygous mutations in Crumbs homolog 1 (CRB1) were identified in a Chinese pedigree with autosomal-recessive retinitis pigmentosa (ARRP) using targeted-capture generation sequencing
After evaluating the significant heredity and impaired protein function, the compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations are the causal genes of early onset ARRP in this pedigree

Summary

Introduction

Retinitis pigmentosa (RP) is a hereditary neurodegenerative retinal disease characterized by progressive loss of photoreceptors. The ocular phenotype of this disease include pigmentary retinopathy, arteriolar narrowing, waxy pallor of the optic disc, cystic macular lesions, cataracts and refractive errors [1,2,3,4,5]. Previous studies showed that the severity of refractive errors in patients with RP was associated with the location of the mutated gene and/or the type of genes involved [5,6,7]. 70% of patients have a positive family history [8]. In the Netherlands, van den Born et al estimated that ~63% of patients with RP had a positive family history, with ~30% inherited in an autosomal-recessive pattern, 22% autosomal-dominant, 10% X-linked and the remaining 37% isolated cases [9]. Gene mutations have been found in www.impactjournals.com/oncotarget

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