MOLECULAR GENETIC ANALYSIS OF NON SYNDROMIC RETINITIS PIGMENTOSA IN INDONESIA USING HIGH RESOLUTION HOMOZYGOSITY MAPPING

Abstract

Backgrounds: Retinitis Pigmentosa (RP) is the most common inherited retinal diseases characterized by poor night vision, visual field contriction and central vision loss at later stage. Understanding on molecular genetics of RP and gene therapy approach has developed tremendously over the past few years. Nevertheless, the number of studies describing the molecular genetics related to RP in the Indonesian population is limited. Objective: To describe the genetic defects responsible for non syndromic RP in Indonesia using high resolution homozygosity mapping Methods: All affected individuals were clinically evaluated. Blood samples of all affected individuals and their family members were obtained. The DNA of all affected patients was analyzed for homozygous regions by Illumina 700K SNP array analysis followed by homozygosity mapping using PLINK software. Known RP genes residing in the identified homozygous regions were analyzed by direct Sanger DNA sequencing. Mutation confirmations were performed using segregation analysis and frequency analysis in ethnically matched healthy controls. Results: In present study, three causative homozygous mutations have been identified in CRB1, RPE65 and RP1 genes. Conclusions: This study revealed three novel mutations in CRB1, RP1 and RPE65 gene as genetic defects responsible for RP in Indonesian families. Mutations in RP1 and RPE65 genes are novel mutations, whereas the CRB1 mutation has been described in the previous study in Indonesian population. The inheritance mode of the RP families is 17.9% and 82.1% are sporadic cases that are still remain unidentified. Keywords: retinitis pigmentosa, high resolution homozygosity mapping, SNP array analysis, mutation