Identification of novel compound heterozygous mutations of USH2A gene in a RP pedigree by targeted-capture next generation sequencing

Abstract

Background RP is the term given to a set of hereditary retinal diseases.RP has groups of clinical characteristics and is a complex disease associated with distinct inheritance patterns.The screening and diagnosis of RP patients is of important significance for the future gene therapy. Objective This study was to characterize the clinical features of a Chinese family with autosomal recessive RP and screen candidate genes. Methods All members of the family underwent complete ophthalmologic examinations.Targeted-capture next generation sequencing (NGS) based molecular genetic analysis was performed on proband to detect mutation.Identified variations were verified in rest family members by PCR and Sanger sequencing.This study was approved by Ethic Committee of Shenzhen Eye Hospital, and written informed consent was obtained from patients prior to any medical examination. Results Proband was diagnosed as RP at 18 years old.His parents and child were asymptomatic.The compound heterozygous mutations in the USH2A gene were identified in the proband, which included c. 9958 G >T (p.Gly3320Cys) mutation and c. 11156 G>A (p.Arg3719His) mutation.The two mutations were inherited from his unaffected parents, respectively. Conclusions The novel compound heterozygous c. 9958 G>T and c. 11156 G>A mutations of USH2A gene are identified as causative mutations of RP in this family.Targeted-capture NGS based eye disease chip can be vital for detecting known RP genes mutations quickly.Targeted-capture NGS can be a new applicable and efficient method for molecular genetic analysis of ocular disease. Key words: Retinitis pigmentosa; Gene; Eye disease chip; Autosomal recessive inheritance